Therapeutic compounds and their use in cancer

ABSTRACT

The invention relates to compounds of Formulae I-III and their therapeutic uses.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional application No.60/799,874 filed May 12, 2006; U.S. Provisional application No.60/822,159 filed Aug. 11, 2006; U.S. Provisional application No.60/865,140 filed Nov. 9, 2006; and U.S. Provisional application No.60/883,707 filed Jan. 5, 2007, each of which is incorporated byreference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

N/A

FIELD OF THE INVENTION

The invention relates to novel compounds and their use to treatdiseases.

BACKGROUND OF THE INVENTION

Cancer is prevalent: In the United States, the probability of developinginvasive cancer is 38% for females and 46% for males that live to be 70years older and older. There will be about 1.4 million new cases ofcancer in 2006. Although the five year survival rate for cancer is now65%, up from about 50% in the mid-nineteen seventies, cancer is deadly.It is estimated that 565,000 people in the United States will die fromcancer in 2006. (American Cancer Society, Surveillance Research, 2006).Although numerous treatments are available for various cancers, the factremains that many cancers remain uncurable, untreatable, and/or becomeresistant to standard therapies. Thus, there is a need for new cancertreatments.

BRIEF SUMMARY OF THE INVENTION

The invention relates to compounds of Formulae I-III below. Theinvention also relates to pharmaceutical compositions having one or morecompounds of Formulae I-III and a pharmaceutically acceptable excipient.The compounds of Formulae I-III were discovered by the inventors to havepharmacological activity. One particular activity the compounds ofFormulae I-III were found to have is anticancer activity.

The invention provides compounds of Formula I wherein:

A is chosen from a substituted or unsubstituted aryl, heteroaryl,heterocyclic, or carbocyclic group;

B is chosen from a substituted or unsubstituted aryl, heteroaryl,heterocyclic, or carbocyclic group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl.

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)_(n)OC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—,—(CH₂)_(n)—O—(CH₂)_(n)—, —(CH₂)_(n)S(CH₂)_(n)—, and—(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n is independently chosen from0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon and/or nitrogencan be optionally substituted with one or more substituentsindependently chosen from hydroxyl, halo, alkoxy, alkyl, amino,cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl, aryl, cycloalkyl,and heterocyclic; wherein —R₂ and —R₃ are independently chosen from —H,alkyl, and —C(═O)OR₄; and wherein R₄ is an alkyl group (e.g., methyl,ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl).

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)_(n)OC(═O)S(CH₂)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, and —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy,alkyl, amino, cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl,aryl, cycloalkyl, and heterocyclic; wherein —R₂ and —R₃ areindependently chosen from —H, alkyl, and —C(═O)OR₄; and wherein R₄ is analkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ortert-butyl).

L₁ and L₂ can be in either orientation, e.g.,—(CH₂)_(n)NC(═S)S(CH₂)_(n)—, refers topurine-(CH₂)_(n)NC(═S)S(CH₂)_(n)-phenyl andpurine-(CH₂)_(n)SC(═S)N(CH₂)_(n)-phenyl orientations unless otherwisespecified.

According to one aspect, A is an aryl group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, —C≡N, —SO₃, and —COOH. In a more specificaspect of the invention, A is a phenyl group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, and —COOH. In an even more specificaspect, A is a phenyl group having one or more substituents chosen from—F, —Cl, —Br, —I, —OCH₃, —CF₃, —CH₃, —OCF₃, —C(═O)CH₃, —COOH, —C≡N, and—NO₂

In one aspect of the compounds of the invention, A is an aryl group withone or more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂—In one specific aspect, A is aphenyl group.

In one aspect of the compounds of the invention, A is a phenyl grouphaving from 1-5 substituents independently chosen from acylamino,acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl,arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio,carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxyl,heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy, isocyanato,isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl,thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl,O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one aspect of the compounds of the invention, B is an arylgroup having one or more substituents chosen from halo, alkyl, alkoxy,haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, —SO₃, and —COOH. Inone specific aspect, B is a phenyl group. In a more specific aspect, Bis a phenyl group having one or more substituents chosen from halo,alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and—COOH. In an even more specific aspect, B is a phenyl group having oneor more substituents chosen from —F, —Cl, —Br, —I, —CH₃, —OCH₃, —CF₃,—OCF₃, —C(═O)CH₃, —COOH, —C≡N, and —NO₂.

In one aspect of the compounds of the invention, B is an aryl group withone or more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, —SO₃, and —NO₂.

In one aspect of the compounds of the invention, B is a phenyl grouphaving from 1-5 substituents independently chosen from acylamino,acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl,arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio,carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxyl,heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy, isocyanato,isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl,thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl,O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzo[1,3]dioxole group. In one aspect of this embodiment, A is a6-bromo-benzo[1,3]dioxol-5-yl group. In one aspect of this embodiment, Ais an unsubstituted benzo[1,3]dioxole group. In one aspect of thisembodiment, A is a 6-iodo-benzo[1,3]dioxol-5-yl group. In one aspect ofthis embodiment, A is a 6-chloro-benzo[1,3]dioxol-5-yl group. In oneaspect of this embodiment, A is a 6-fluoro-benzo[1,3]dioxol-5-yl group.In one aspect of this embodiment, A has from 1-5 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedindanone group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstituted indanegroup. In one aspect of this embodiment, A has from 1-5 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzo[1,4]dioxane group. In one aspect of this embodiment, A has from1-5 substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzoxazinone group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzoxazine group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzodioxine group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutednaphthyl group. In one aspect of this embodiment, A has from 1-6substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstituted pyrrolegroup. In one aspect of this embodiment, A has from 1-3 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.According to one aspect A is unsubstituted.

According to one embodiment, A is a substituted or unsubstitutedpyridine group. In one aspect of this embodiment, A has from 1-4substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,A is unsubstituted.

According to one embodiment, A is a substituted or unsubstitutedcyclohexyl group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,A is unsubstituted.

According to one embodiment, B is a substituted or unsubstitutedbenzo[1,3]dioxole group. In one aspect of this embodiment, B is a6-bromo-benzo[1,3]dioxol-5-yl group. In one aspect of this embodiment, Bis an unsubstituted benzo[1,3]dioxole group. In one aspect of thisembodiment, B is a 6-iodo-benzo[1,3]dioxol-5-yl group. In one aspect ofthis embodiment, B is a 6-chloro-benzo[1,3]dioxol-5-yl group. In oneaspect of this embodiment, B is a 6-fluoro-benzo[1,3]dioxol-5-yl group.In one aspect of this embodiment, B has from 1-4 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, B is a substituted or unsubstitutednaphthyl group. In one aspect of this embodiment, B has from 1-6substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,B is unsubstituted.

According to one embodiment, B is a substituted or unsubstituted pyrrolegroup. In one aspect of this embodiment, B has from 1-3 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.According to one aspect of this embodiment, B is unsubstituted.

According to one embodiment, B is a substituted or unsubstitutedpyridine group. In one aspect of this embodiment, B has from 1-4substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,B is unsubstituted.

According to one embodiment, B is a substituted or unsubstitutedcyclohexyl group. In one aspect of this embodiment, B has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,B is unsubstituted.

According to one aspect of the invention, compounds of Formula I areprovided wherein:

A is a substituted or unsubstituted aryl group;

B is a substituted or unsubstituted aryl group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl.

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups;

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups; and pharmaceutically acceptable saltsthereof.

According to one aspect of the invention, compounds of Formula I areprovided wherein:

A is a substituted or unsubstituted heteroaryl group;

B is a substituted or unsubstituted aryl group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl;

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups;

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups; and pharmaceutically acceptable saltsthereof.

According to one aspect of the invention, compounds of Formula I areprovided wherein A is a substituted or unsubstituted aryl group; B is asubstituted or unsubstituted heteroaryl group; R1 is chosen from hydro,alkyl, aryl, heteroaryl, amino, halo, sulfur, and thioalkyl; andpharmaceutically acceptable salts thereof.

According to one aspect of the invention, compounds of Formula I areprovided wherein A is a substituted or unsubstituted heterocyclic group;B is a substituted or unsubstituted aryl group; and R1 is chosen fromhydro, alkyl, aryl, heteroaryl, alkyl amino, halo, sulfur, andthioalkyl.

According to one aspect of the invention, compounds of Formula I areprovided wherein A is a substituted or unsubstituted aryl group; B is asubstituted or unsubstituted heterocyclic group; R1 is chosen fromhydro, alkyl, aryl, heteroaryl, amino, halo, sulfur, and thioalkyl.

According to some aspects of the invention, in the compound of FormulaI, A is substituted or unsubstituted and chosen from indazolyl,1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzooxazolyl,1H-benzoimadazolyl, 3H-benzooxazol-2-one, 4H-benzo[1,4]oxazin-3-one, 1,3dihydro-benzoimadazol-2-one, 3H-benzothialo-2-one,1H-pyrazolo[3,4-b]pyridine, 1H-quinaxolin-2-one, 1H-quinaxolin-2-one,4H-benzo[1,4]oxazin-3-one, isoquinoline, indoline, 1,3dihydro-indol-2-one, 2,3-dihydro-benzo[1,4]dioxine, thienyl(thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl,furyl (furanyl), isobenzofuranyl, chromenyl, xanthenyl, phenoxanthiinyl,pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl),2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,indolizinyl, isoindolyl, 3H-indolyl, indolyl, purinyl, 4H-quinolizinyl,isoquinolyl, quinolyl, phthalzinyl, naphthyridinyl, quinozalinyl,cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl,acrindinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl,phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl,1,4-dihydroquinoxaline-2,3-dione, 7 aminoisocoumarin,pyrido[1,2-a]pyrimidin-4-one, pyrazolo[1,5-a]pyrimidinyl,pyrazolo[1,5-a]pyrimidin-3-yl, 1,2-benzoisoxazol-3-yl, benzimidazolyl,2-oxindolyl, 2 oxobenzimidazolyl, tetrahydrofuranyl, pyranyl,piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl,indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl,chromanyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

According to some aspects of the invention, in the compound of FormulaI, B is substituted or unsubstituted and chosen from indazolyl,1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzooxazolyl,1H-benzoimadazolyl, 3H-benzooxazol-2-one, 4H-benzo[1,4]oxazin-3-one, 1,3dihydro-benzoimadazol-2-one, 3H-benzothialo-2-one,1H-pyrazolo[3,4-b]pyridine, 1H-quinaxolin-2-one, 1H-quinaxolin-2-one,4H-benzo[1,4]oxazin-3-one, isoquinoline, indoline, 1,3dihydro-indol-2-one, 2,3-dihydro-benzo[1,4]dioxine, thienyl(thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl,furyl (furanyl), isobenzofuranyl, chromenyl, xanthenyl, phenoxanthiinyl,pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl),2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,indolizinyl, isoindolyl, 3H-indolyl, indolyl, purinyl, 4H-quinolizinyl,isoquinolyl, quinolyl, phthalzinyl, naphthyridinyl, quinozalinyl,cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl,acrindinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl,phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl,1,4-dihydroquinoxaline-2,3-dione, 7 aminoisocoumarin,pyrido[1,2-a]pyrimidin-4-one, pyrazolo[1,5-a]pyrimidinyl,pyrazolo[1,5-a]pyrimidin-3-yl, 1,2-benzoisoxazol-3-yl, benzimidazolyl,2-oxindolyl, 2 oxobenzimidazolyl, tetrahydrofuranyl, pyranyl,piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl,indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl,chromanyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

In some aspects of the compounds of the invention, the A ring issubstituted with one or more substituents chosen from -L₁-C(═O)OH,-L₁-CH═CHC(═O)OH, -L₁-C(═O)NH₂, -L₁-C(═O)NH(C₁₋₃ alkyl), -L₁-C(═O)N(C₁₋₃alkyl)₂, -L₁-S(═O)₂(C₁₋₃alkyl), -L₁-S(═O)₂NH₂, -L₁-S(═O)₂N(C₁₋₃ alkyl)₂,-L₁-S(═O)₂NH(C₁₋₃ alkyl), -L₁-C(═O)NHOH, -L₁—C(═O)CH₂NH₂,-L₁-C(═O)CH₂OH, -L₁-C(═O)CH₂SH, -L₁-C(═O)NHCN, -L₁-NHC(═O)OR_(o),-L₁-C(═O)NHR_(o), -L₁-NH(C═O)NHR_(o), -L₁-C(═O)N(R_(o))₂,-L₁-NH(C═O)N(R_(o))₂, -L₁-sulfo; where R_(o) is chosen from alkyl andhaloalkyl, and L₁ is independent of any other L, in the compound and isdefined as above.

In some aspects of the compounds of the invention, the B ring issubstituted with one or more substituents chosen from -L₁-C(═O)OH,-L₁-CH═CHC(═O)OH, -L₁-C(═O)NH₂, -L₁-C(═O)NH(C₁₋₃ alkyl), -L₁-C(═O)N(C₁₋₃alkyl)₂, -L₁-S(═O)₂(C₁₋₃alkyl), -L₁-S(═O)₂NH₂, -L₁-S(═O)₂N(C₁₋₃ alkyl)₂,-L₁-S(═O)₂NH(C₁₋₃ alkyl), -L₁-C(═O)NHOH, -L₁—C(═O)CH₂NH₂,-L₁-C(═O)CH₂OH, -L₁-C(═O)CH₂SH, -L₁-C(═O)NHCN, -L₁-NHC(═O)OR_(o),-L₁-C(═O)NHR_(o), -L₁-NH(C═O)NHR_(o), -L₁-C(═O)N(R_(o))₂,-L₁-NH(C═O)N(R_(o))₂, -L₁-sulfo; where R_(o) is chosen from alkyl andhaloalkyl, and L₁ is independent of any other L, in the compound and isdefined as above.

According to one aspect of the compounds of the invention, L₁ is chosenfrom —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂, —CH(CH₃)CH₂—, —CH(CH₂CH₃)CH₂—,—CH(CH(CH₃)₂)CH₂—, —C(CH₂CH₂)CH₂—, —C(CH₂CH₂CH₂)CH₂—,—CH(CH(CH₃)CH₂CH₃)CH₂—, —CH(CH(CH₂)₄)CH₂—, —CH(CH(CH₂)₅)CH₂—,—CH(OH)CH₂—, and —CH(CH₂OH)CH₂—In a more specific aspect L₁ is chosenfrom —CH₂CH₂— and —CH₂CH₂CH₂—In an even more specific aspect, L₁ is—CH₂CH₂—. L₁ can be in either orientation, e.g., —CH(CH₂CH₂)CH₂-refersto purine-CH(CH₂CH₂)CH₂-phenyl and purine-CH₂CH(CH₂CH₂)-phenylorientations unless otherwise specified.

According to one aspect of the invention, compounds of Formula I areprovided where L₂ is chosen from —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂,—CH(CH₃)CH₂—, —CH(CH₂CH₃)CH₂—, —CH(CH(CH₃)₂)CH₂—, —C(CH₂CH₂)CH₂—,—C(CH₂CH₂CH₂)CH₂—, —CH(CH(CH₃)CH₂CH₃)CH₂—, —CH(CH(CH₂)₄)CH₂—,—CH(CH(CH₂)₅)CH₂—, —CH(OH)CH₂—, and —CH(CH₂OH)CH₂—. In a more specificaspect L₂ is chosen from —CH₂CH₂— and —CH₂CH₂CH₂—. In an even morespecific aspect L₂ is —CH₂CH₂—. L₂ can be in either orientation, e.g.,—CH(CH₂CH₂)CH₂— refers to e.g, purine-CH(CH₂CH₂)CH₂-phenyl andpurine-CH₂CH(CH₂CH₂)-phenyl orientations unless otherwise specified.

According to one aspect of the compounds of the invention, A is a groupchosen from 2,5-dimethoxyphenyl, 2,5-diethoxyphenyl,2,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-chlorophenyl, and4-benzonitrile. In this aspect, the positions (numbering) of thesubstituents are relative to the linkage of the phenyl group to thepurine core. In a specific embodiment of this aspect L₁ is —S—.

According to one aspect of the compounds of the invention, B is a groupchosen from 2-bromophenyl, 2-fluorophenyl, 2-chlorophenyl,3-fluorophenyl, 3-iodophenyl, 3-bromophenyl, 4-fluorophenyl,4-chlorophenyl, 4-bromophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl,2,6-dichlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl,4-chloro-2-fluorophenyl, 2-chloro-6-fluorophenyl, pentafluorophenyl,2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-benzoic acid,2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl,3-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl,3,4,5-trimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, p-tolyl, o-tolyl,2,5-dimethylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl,4-phenylethanone, 4-phenol, 4-benzenesulfonic acid,4-dimethylaminophenyl, 4-carbamic acid tert-butyl ester phenyl,4-aminophenyl, 3-trifluoromethoxyphenyl, and 3,5bistrifluoromethylphenyl. In this aspect, the positions (numbering) ofthe substituents are relative to the linkage of the phenyl group to thepurine core. In a specific embodiment of this aspect, L₂ is chosen from—CH₂—CH₂— and —CH₂—CH₂—CH₂—.

The invention also provides compounds of Formula II where the variablesare as in any of the above embodiments and aspects of the invention forthe compounds of Formula I.

The invention also provides compounds of Formula III where the variablesare as in any of the above embodiments and aspects of the invention forthe compounds of Formula I.

According to one aspect of the invention, compounds of Formula I areprovided wherein:

A is a substituted or unsubstituted heterocyclic group;

B is a substituted or unsubstituted aryl group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl;

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups;

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups; and pharmaceutically acceptable saltsthereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl or heterocyclic group;

B can be substituted or unsubstituted and is chosen from a heteroaryl orheterocyclic group having one or more hetero atoms chosen from —N—, —O—,—S—, and —P—;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In another aspect of the invention, A can be substituted orunsubstituted and is chosen from a benzo[1,3]dioxole or phenyl group;

B can be a substituted or unsubstituted heteroaryl or heterocyclic grouphaving one or more hetero atoms chosen from —N—, —O—, —S—, and —P—;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is a group chosen from 5-halo-benzo[1,3]dioxole (e.g,5-bromo-benzo[1,3]dioxole), dimethoxybenzene (e.g.,1,4-dimethoxybenzene, 2,3-dimethoxybenzene, and 2,4-dimethoxybenzene),and diethoxybenzene (e.g., 1,4-diethoxybenzene, 2,3-diethoxybenzene, and2,4-diethoxybenzene);

B can be substituted or unsubstituted and is chosen from a heteroaryl orheterocyclic group having one or more hetero atoms chosen from —N—, —O—,—S—, and —P—;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

B can be substituted or unsubstituted and is a heterocyclic group chosenfrom piperidine, pyrrolidine, azetidine, piperazine, morpholine, andtetrahydro-pyran;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are defined as above; and pharmaceutically acceptable saltsthereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

B is a group chosen from piperidine, piperidine-1-carboxylic acid ethylester, piperidine-1-carboxylic acid tert-butyl ester,2,2,6,6-tetramethyl-piperidine, piperidine-2,6-dione,piperidine-1-carbaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine,tetrahydro-pyran, adamantane, piperidine-1-carbaldehyde,1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine,1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine,piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylicacid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester,1-pyrrolidin-1-yl-ethanone, 1-methanesulfonyl-pyrrolidine,pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butylester, 1-methyl-azetidine, azetidine, azetidine-1-carbaldehyde,1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole,undecafluorocyclohexane, cyclohexyl-carbamic acid tert-butyl ester,1-piperazin-1-yl-ethanone, 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene,5-methyl 2,4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzylester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester,piperidine-1,2-dicarboxylic acid 1-tert butyl ester 2-ethyl ester,benzyl-1,2,3,6-tetrahydro-pyridine,hexahydro-4b-aza-cyclopropa[cd]pentalene,2-isopropyl-piperidine-1carboxylic acid tert-butyl ester,piperidine-1-carboxylic acid ethyl amide, piperidine-1-carboxylic acidisopropyl amide, piperidine-1-carboxylic acid tert-butyl amide,[{piperidine-1-carbonyl}amino]-acetic acid ethyl ester, isopropylpiperidine, isobutyl piperidine,2,2-dimethyl-1-piperidin-1-yl-propan-1-one,2,2-dimethyl-1-piperidin-1-yl-butan-1-one, 2-isopropyl-piperidine,1-isopropyl piperazine, and 1-cyclopentyl-piperazine.

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B can be substituted or unsubstituted and is a heteroaryl orheterocyclic group chosen from piperidine, pyrrolidine, azetidine,piperazine, morpholine, and tetrahydro-pyran.

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B is a group chosen from piperidine, piperidine-1-carboxylic acid ethylester, piperidine-1-carboxylic acid tert-butyl ester,2,2,6,6-tetramethyl-piperidine, piperidine-2,6-dione,piperidine-1-carbaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine,tetrahydro-pyran, adamantane, piperidine-1-carbaldehyde,1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine,1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine,piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylicacid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester,1-pyrrolidin-1-yl-ethanone, 1-methanesulfonyl-pyrrolidine,pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butylester, 1-methyl-azetidine, azetidine, azetidine-1-carbaldehyde,1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole,undecafluorocyclohexane, cyclohexyl-carbamic acid tert-butyl ester,1-piperazin-1-yl-ethanone, 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene,5-methyl 2,4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzylester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester,piperidine-1,2-dicarboxylic acid 1-tert butyl ester 2-ethyl ester,benzyl-1,2,3,6-tetrahydro-pyridine,hexahydro-4b-aza-cyclopropa[cd]pentalene,2-isopropyl-piperidine-1carboxylic acid tert-butyl ester,piperidine-1-carboxylic acid ethyl amide, piperidine-1-carboxylic acidisopropyl amide, piperidine-1-carboxylic acid tert-butyl amide,[{piperidine-1-carbonyl}amino]-acetic acid ethyl ester, isopropylpiperidine, isobutyl piperidine,2,2-dimethyl-1-piperidin-1-yl-propan-1-one,2,2-dimethyl-1-piperidin-1-yl-butan-1-one, 2-isopropyl-piperidine,1-isopropyl piperazine, and 1-cyclopentyl-piperazine;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A is a group chosen from5-halo-benzo[1,3]dioxole, dimethoxybenzene, and diethoxybenzene;

B is a group chosen from piperidine, piperidine-1-carboxylic acid ethylester, piperidine-1-carboxylic acid tert-butyl ester,2,2,6,6-tetramethyl-piperidine, piperidine-2,6-dione,piperidine-1-carbaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine,tetrahydro-pyran, adamantane, piperidine-1-carbaldehyde,1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine,1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine,piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylicacid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester,1-pyrrolidin-1-yl-ethanone, 1-methanesulfonyl-pyrrolidine,pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butylester, 1-methyl-azetidine, azetidine, azetidine-1-carbaldehyde,1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole,undecafluorocyclohexane, cyclohexyl-carbamic acid tert-butyl ester,1-piperazin-1-yl-ethanone, 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene,5-methyl 2,4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzylester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester,piperidine-1,2-dicarboxylic acid 1-tert butyl ester 2-ethyl ester,benzyl-1,2,3,6-tetrahydro-pyridine,hexahydro-4b-aza-cyclopropa[cd]pentalene,2-isopropyl-piperidine-1carboxylic acid tert-butyl ester,piperidine-1-carboxylic acid ethyl amide, piperidine-1-carboxylic acidisopropyl amide, piperidine-1-carboxylic acid tert-butyl amide,[{piperidine-1-carbonyl}amino]-acetic acid ethyl ester, isopropylpiperidine, isobutyl piperidine,2,2-dimethyl-1-piperidin-1-yl-propan-1-one,2,2-dimethyl-1-piperidin-1-yl-butan-1-one, 2-isopropyl-piperidine,1-isopropyl piperazine, and 1-cyclopentyl-piperazine;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

According to one aspect of the invention, in the compounds of Formula I,A is an aryl or heterocyclic group having one or more substituentschosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—C(═O)alkyl, hydroxyl, —C≡N, —SO₃, and —COOH. In a more specific aspectA is a phenyl group having one or more substituents chosen from halo,alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and—COOH. In another specific aspect, A is a phenyl group having one ormore substituents chosen from —F, —Cl, —Br, —I, —OCH₃, and —OCH₂CH₃. Inanother aspect A is a benzo[1,3]dioxole group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, and —COOH. In another specific aspect, Ais a benzo[1,3]dioxole group having one or more substituents chosen from—F, —Cl, —Br, —I, —OCH₃, and —OCH₂CH₃.

In one aspect, in the compounds of Formula I, A is an aryl orheterocyclic group with one or more substituents chosen from hydroxyl,halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂. In onespecific aspect, A is a phenyl group having one or more substituentschosen from hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl),—C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN,—NH₂, and —NO₂. In another specific aspect, A is a benzo[1,3]dioxolegroup having one or more substituents chosen from hydroxyl, halo, alkyl,alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl),—C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₁₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂.

In one aspect, in the compounds of Formula I, A is a phenyl orbenzo[1,3]dioxole group having from 1-5 substituents independentlychosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio,alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy,aryloxy, arylthio, carbocycle, cyano, cyanato, halo, haloalkyl,halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one aspect, in the compounds of Formula I, B is aheterocyclic group having one or more heteroatoms chosen from —N— and—O— wherein the heterocyclic group can have one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), amino acid (chosen fromnatural and non-natural amino acids), peptide having 1-5 amino acidresidues (chosen from natural and non-natural amino acids), —C(═O)alkylwhere the alkyl is substituted with one or more substituents (chosenfrom alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano,hydroxyl, —COOH (and esters thereof), sulfonyl, sulfonamide) andsulfonyl. In one specific aspect, B is a piperidine (piperidinyl) group.In one specific aspect, B is a piperidine group substituted with one ormore substituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl. In a more specific aspect, B is apiperidine group having one or more substituents chosen from hydro,halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (andesters thereof), and sulfonyl. In an even more specific aspect, B is apiperidine group having one or more substituents chosen from —C(═O),—C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is a homopiperidine (homopiperidinyl) group.In a more specific aspect, B is a homopiperidine group having one ormore substituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl. In an even more specific aspect, Bis a homopiperidine group having one or more substituents chosen from—C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is a piperazine (piperazinyl) group. In a morespecific aspect, B is a piperazine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), amino acid (chosen fromnatural and non-natural amino acids), peptide having 1-5 amino acidresidues (chosen from natural and non-natural amino acids), —C(═O)alkylwhere the alkyl is substituted with one or more substituents (chosenfrom alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano,hydroxyl, —COOH (and esters thereof), sulfonyl, sulfonamide) andsulfonyl. In an even more specific aspect, B is a piperazine grouphaving one or more substituents chosen from —C(═O), —C(═O)CH₃, —CH₃,—CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃,—C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is a pyrrolidine (pyrrolidinyl) group. In amore specific aspect, B is a pyrrolidine group having one or moresubstituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl. In an even more specific aspect, Bis a pyrrolidine group having one or more substituents chosen from—C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is an azetidine (azetidinyl) group. In a morespecific aspect, B is an azetidine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), amino acid (chosen fromnatural and non-natural amino acids), peptide having 1-5 amino acidresidues (chosen from natural and non-natural amino acids), —C(═O)alkylwhere the alkyl is substituted with one or more substituents (chosenfrom alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano,hydroxyl, —COOH (and esters thereof), sulfonyl, sulfonamide) andsulfonyl. In an even more specific aspect, B is an azetidine grouphaving one or more substituents chosen from —C(═O), —C(═O)CH₃, —CH₃,—CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃,—C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one aspect of the compounds of Formula I, B is a heterocyclic groupwith one or more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, —SO₃, and —NO₂. In a specific aspect, Ba group is chosen piperidine, piperazine, pyrrolidine, azetidine,tetrahydro-pyran, and morpholine group, each having one or moresubstituents. In a more specific aspect, B is a piperidine group havingone or more substituents.

In one aspect, B is a group chosen from piperidine, piperazine,pyrrolidine, azetidine, tetrahydro-pyran, and morpholine, wherein said Bgroup can have from 1-5 substituents independently chosen fromacylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino,aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy,arylthio, carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl,hydroxyl, heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy,isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide,thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl,N-carbamyl, O-thio carbamyl, N-thiocarbamyl, and C-amido. In a morespecific aspect, B is a piperidine group having one or moresubstituents.

According to one embodiment, A is a substituted or unsubstitutedbenzo[1,3]dioxole group. In one aspect of this embodiment, A is a5-bromo-benzo[1,3]dioxole group. In one aspect of this embodiment, A isan unsubstituted benzo[1,3]dioxole group. In one aspect of thisembodiment, A is a 5-iodo-benzo[1,3]dioxole group. In one aspect of thisembodiment, A is a 5-chloro-benzo[1,3]dioxole group. In one aspect ofthis embodiment, A is a 5-fluoro-benzo[1,3]dioxole group. In one aspectof this embodiment, A has from 1-5 substituents independently chosenfrom acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl,amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy,arylthio, carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl,hydroxyl, heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy,isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide,thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl,N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

In one aspect of the invention, A is substituted with one or moresubstituents and is a group chosen from a phenyl, benzo[1,3]dioxole,indanone, group; B is substituted with one or more substituents and is agroup chosen from piperidine, piperazine, pyrrolidine, azetidine,tetrahyro-pyran, and morpholine; R₁ is a hydro; L₁ is —S—; L₂ is—CH₂CH₂—, and pharmaceutically acceptable salt thereof. According tothis aspect of the invention, the A group substituents are chosen fromhalo, —CN, alkoxy, and the B group substituents are chosen from —C(═O),—C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl and heterocyclic group;

B can be substituted or unsubstituted and is chosen from a cycloalkyland heterocyclic group;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In another aspect of the invention, A can be substituted orunsubstituted and is chosen from a benzo[1,3]dioxole and phenyl group;

B can be substituted or unsubstituted and is chosen from a heteroaryl,heterocyclic, and cycloalkyl group;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is a group chosen from 5-halo-benzo[1,3]dioxole (e.g.,5-bromo-benzo[1,3]dioxole), dimethoxybenzene (e.g.,1,4-dimethoxybenzene, 2,3-dimethoxybenzene, and 2,4-dimethoxybenzene),and diethoxybenzene (e.g., 1,4-diethoxybenzene, 2,3-diethoxybenzene, and2,4-diethoxybenzene);

B can be substituted or unsubstituted and is chosen from a cycloalkyl,heteroaryl, and heterocyclic group;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

B can be substituted or unsubstituted and is a group chosen fromcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl,oxepanyl (oxepane), tetrahydro-thiophenyl (tetrahydro-thiophene),thiopyranyl, thiepanyl (thiepane), and tetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are defined as above; and pharmaceutically acceptable saltsthereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

-L₂-B is a group chosen from (1-Cyclopropyl-propyl)-carbamic acidtert-butyl ester, [1-(Tetrahydro-thiopyran-4-yl)-propyl]-carbamic acidtert-butyl ester, (1-Cyclohexyl-propyl)-carbamic acid tert-butyl ester,(1-Cyclobutyl-propyl)-carbamic acid tert-butyl ester,N-(1-Cyclopropyl-propyl)-methanesulfonamide,1-(1-Cyclopropyl-propyl)-3-isopropyl-urea,(1-Cyclopentyl-propyl)-carbamic acid tert-butyl ester,[1-(Tetrahydro-pyran-4-yl)-propyl]-carbamic acid tert-butyl ester,1-Cyclopropyl-propylamine, 1-Cyclohexyl-propylamine,1-Cyclobutyl-propylamine, 1-Cyclopentyl-propylamine,1-(Tetrahydro-pyran-4-yl)-propylamine,1-(Tetrahydro-thiopyran-4-yl)-propyl amine, and1-(1-Cyclohexyl-propyl)-1H-pyrrole;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ is as defined above; and pharmaceutically acceptable salts thereof.

In some specific aspects of the invention, L₂ is as defined above andhas one or more substituents chosen from hydroxyl, halo, alkoxy, amino,C₁₋₃ alkyl, C₃₋₇ cycloalkyl, —N—C(═O)OC(CH₃)₃, —NSO₂CH₃,—NC(═O)NC(CH₃)₂, and pyrrolyl.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B can be substituted or unsubstituted and is a heteroaryl orheterocyclic group chosen from cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B is a group chosen from cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A is a group chosen from5-halo-benzo[1,3]dioxole, dimethoxybenzene, and diethoxybenzene;

B is a group chosen cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

According to one aspect of the invention, in the compounds of Formula I,A is an aryl or heterocyclic group having one or more substituentschosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—C(═O)alkyl, hydroxyl, —C≡N, —SO₃, and —COOH. In another specificaspect, A is a phenyl group having one or more substituents chosen fromhalo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl,hydroxyl, and —COOH. In another specific aspect, A is a phenyl grouphaving one or more substituents chosen from —F, —Cl, —Br, —I, —OCH₃, and—OCH₂CH₃. In another aspect, A is a benzo[1,3]dioxole group having oneor more substituents chosen from halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and —COOH. In another specificaspect, A is a benzo[1,3]dioxole group having one or more substituentschosen from —F, —Cl, —Br, —I, —OCH₃, and —OCH₂CH₃.

In one aspect, in the compounds of Formula I, A is an aryl orheterocyclic group with one or more substituents chosen from hydroxyl,halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂. In onespecific aspect, A is a phenyl group having one or more substituentschosen from hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl),—C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN,—NH₂, and —NO₂. In another specific aspect, A is a benzo[1,3]dioxolegroup having one or more substituents chosen from hydroxyl, halo, alkyl,alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl),—C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂.

In one specific aspect of the compounds of the invention, B is acycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, or cycloheptyl)group. In another specific aspect, B is a cycloalkyl group having one ormore substituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), and sulfonyl. In anotherspecific aspect, B is a cycloalkyl group having one or more substituentschosen from —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In one specific aspect of the compounds of the invention, B is athiopyranyl group. In another specific aspect, B is a thiopyranyl grouphaving one or more substituents chosen from hydro, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl,cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof), and sulfonyl. Inanother specific aspect, B is a thiopyranyl group having one or moresubstituents chosen from —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃,—C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃,—C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂, —C(═O)NHCH₂CH₃,—C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃, —C(═O)NHCH₂C(═O)OCH₂CH₃,—C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —C(═O)CH₂C(CH₃)₃, cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In one specific aspect of the compounds of the invention, B is atetrahydro-pyranyl group. In another specific aspect, B is atetrahydro-pyranyl group having one or more substituents chosen fromhydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (andesters thereof), and sulfonyl. In another specific aspect, B is atetrahydro-pyranyl group having one or more substituents chosen from—C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In one aspect, B is a group chosen cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl, wherein said B group can have from 1-5 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

In one aspect of the invention, A is substituted with one or moresubstituents and is a group chosen from a phenyl or benzo[1,3]dioxolegroup; B is substituted with one or more substituents and is a groupchosen from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl,thiopyranyl, and tetrahydro-pyranyl;

R₁ is a hydro; L₁ is —S—; L₂ is —CH₂CH₂—, and pharmaceuticallyacceptable salt thereof. According to this aspect of the invention, theA group substituents are chosen from halo and alkoxy, and the B groupsubstituents are chosen from —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃,—CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃,—C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂, —C(═O)NHCH₂CH₃,—C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃, —C(═O)NHCH₂C(═O)OCH₂CH₃,—C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —C(═O)CH₂C(CH₃)₃, cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In one aspect, the invention provides compounds of Formula I wherein R1is hydro.

In one aspect, the invention provides compounds of Formula I wherein L₁is —S—.

In one aspect, the invention provides compounds of Formula I whereinL₂-CH₂CH₂—.

In one aspect, the invention provides compounds of Formula I, whereinthe B ring is an optionally substituted admantane ring.

In one aspect, the invention provides compounds of Formula I wherein L₂is —(CH₂), —(CH₂)_(n)—, and each n is independently chosen from 0, 1, 2,and 3 and wherein each carbon can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy,alkyl, amino, cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl,aryl, cycloalkyl, and heterocyclic; wherein —R₂ and —R₃ areindependently chosen from —H, alkyl, and —C(═O)OR₄; and wherein R₄ is analkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ortert-butyl).

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the presentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

Other features and advantages of the invention will be apparent from thefollowing detailed description, and from the claims.

DETAILED DESCRIPTION OF THE INVENTION 1. Definitions

As used herein, “acylamino” (or “acylamido”) groups are any C1-6 acyl(alkanoyl) as defined herein, attached to an amino nitrogen, e.g.,acetamido, chloroacetamido, propionamido, butanoylamido, pentanoylamidoand hexanoylamido, as well as aryl-substituted C1-6 acylamino groups,e.g., benzoylamido, and pentafluorobenzoylamido.

As used herein, “acyloxy” groups are any C1-6 acyl (alkanoyl) as definedherein, attached to an oxy (—O—) group, e.g., formyloxy, acetoxy,propionoyloxy, butanoyloxy, pentanoyloxy and hexanoyloxy.

As used herein, the term “alkenyl” refers to, by itself or as part ofanother group, a straight or branched chain radical of 2-10 carbonatoms, unless the chain length is limited thereto, including at leastone double bond between two of the carbon atoms in the chain. Typicalnon-limiting examples of alkenyl groups include ethenyl, 1-propenyl,2-propenyl, 2-methyl-1-propenyl, 1-butenyl and 2-butenyl.

As used herein, the term “alkoxy” refers to both an —O-alkyl and an—O-cycloalkyl group, as defined herein. Lower alkoxy refers to —O-loweralkyl groups. Non-limiting alkoxy groups include oxygen substituted byone of the C₁₋₁₀ alkyl groups mentioned above, which may be optionallysubstituted. Alkoxy substituents include, without limitation, halo,morpholino, amino including alkylamino and dialkylamino, and carboxyincluding esters thereof.

As used herein, the term “alkyl” refers to a saturated aliphatichydrocarbon including straight chain and branched chain groups. In oneaspect, the alkyl group has 1 to 20 carbon atoms (whenever it appearsherein, a numerical range such as “1 to 20” refers to each integer inthe given range; e.g., “1 to 20 carbon atoms” means that the alkyl groupmay consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. up toand including 20 carbon atoms). In another aspect, it is a medium sizealkyl having 1 to 10 carbon atoms. In yet another aspect, it is a loweralkyl having 1 to 6 carbon atoms, and even more preferably 1 to 4 carbonatoms. The alkyl group may be substituted or unsubstituted. Whensubstituted, the substituent group(s) can be one or more independentlychosen from cycloalkyl, aryl, heteroaryl, heterocyclic, hydroxy, alkoxy,aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl,thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl,C-amido, N-amido, C-carboxy, O-carboxy, cyanato, isocyanato,thiocyanato, isothiocyanato, nitro, silyl, and amino. Typicalnon-limiting examples of C₁₋₁₀ alkyl groups include methyl, ethyl,propyl, isopropyl, butyl, sec butyl, tert butyl, pentyl, hexyl and octylgroups, which may be optionally substituted.

As used herein, the term “alkylthio” group refers to both an S-alkyl andan —S-cycloalkyl group, as defined herein. Non-limiting alkylthio groupsinclude sulfur substituted by one of the C₁₋₁₀ alkyl groups mentionedabove, which may be optionally substituted. Also included are thesulfoxides and sulfones of such alkylthio groups.

As used herein, the term “alkynyl” refers to a straight or branchedchain radical of 2-10 carbon atoms, unless the chain length is limitedthereto, wherein there is at least one triple bond between two of thecarbon atoms in the chain. Typical alkynyl groups include ethynyl,1-propynyl, 1-methyl-2-propynyl, 2-propynyl, 1-butynyl and 2-butynyl.

As used herein, the term “amino” refers to an —NR₁₇R₁₈ group, with R₁₇and R₁₈ being hydro to give an —NH₂ group. Independently, R₁₇ and R₁₈may also be hydro, C₁₋₁₀ alkyl or cycloalkyl groups, or R₁₇ and R₁₇ arecombined with the N to form a ring structure, such as a piperidine, orR₁₇ and R₁₈ are combined with the N to form a ring, such as apiperazine. One of R₁₇ and R₁₈ can be hydro and the other alkyl orcycloalkyl. The alkyl or cycloalkyl group may be optionally substituted.

As used herein, the term “amino acid” refers to natural and non-naturalamino acids. Examples of natural amino acids include, but are notlimited, Alanine, arginine, asparagine, aspartic acid, cysteine,glutamic acid, glutamine, glycine, histidine, isoleucine, leucine,lysine, methionine, phenylalanine, proline, serine, threonine,tryptophan, tyrosine, valine, and protected versions thereof (e.g.,boc). Examples of non-natural amino acids include, but are not limitedto, O-methyl-L-tyrosine, an L-3-(2-naphthyl)alanine, a3-methyl-phenylalanine, an O-4-allyl-L-tyrosine, a 4-propyl-L-tyrosine,a tri-O-acetyl-GlcNAcβ-serine, an L-Dopa, a fluorinated phenylalanine,an isopropyl-L-phenylalanine, a p-azido-L-phenylalanine, ap-acyl-L-phenylalanine, a p-benzoyl-L-phenylalanine, an L-phosphoserine,a phosphonoserine, a phosphonotyrosine, a p-iodo-phenylalanine, ap-bromophenylalanine, a p-amino-L-phenylalanine, and anisopropyl-L-phenylalanine.

As used herein, the term “aryl” refers to, by itself or as part, ofanother group a monocyclic, bicyclic or tricyclic aromatic groupscontaining from 6 to 14 carbons in the ring portion. Non-limiting arylgroups include C6-14 aryl, preferably C6-10 aryl. Typical C6-14 arylgroups include phenyl, naphthyl, phenanthrenyl, anthracenyl, indenyl,azulenyl, biphenyl, biphenylenyl and fluorenyl groups.

As used herein, the term “arylalkyl” refers to any of the C1-10 alkylgroups substituted by any of the above-mentioned C6-14 aryl groups asdefined herein. Non-limiting examples of arylalkyl group include benzyl,phenethyl, and naphthylmethyl.

As used herein, the term “arylalkenyl” is used herein to mean any of theabove-mentioned C2-10 alkenyl groups substituted by any of theabove-mentioned C6-14 aryl groups.

As used herein, the term “arylalkynyl” refers to any of C2-10 alkynylgroups substituted by any of the above-mentioned C6-14 aryl groups asdefined herein.

As used herein, the term “arylalkoxy” refers to any of the C1-10 alkoxygroups substituted by any of the aryl groups as defined herein, whichmay be optionally substituted. Examples of arylalkoxy groups includebenzyloxy and phenethyloxy.

As used herein, the term “aryloxy” refers to oxygen substituted by anyof the C6-14 aryl groups defined herein, which may be optionallysubstituted. Examples of aryloxy groups include phenoxy and4-methylphenoxy.

As used herein, the term “arylthio” group refers to both an —S-aryl andan —S-heteroaryl group, as defined herein.

As used herein, the term “carbocycle” or “carbocyclic” refers tocycloalkyl and partially saturated carbocyclic groups. Non-limitingcarbocyclic groups are C3-8 cycloalkyl and cycloalkenyl. Typicalcycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cyclohexenyl, and cycloheptyl.

As used herein, the term “cyano” refers to a —C≡N group.

As used herein, the term “cyanato” refers to a —CNO group.

As used herein, the term “halo” or “halogen group” refers to a fluoro,chloro, bromo and iodo group.

As used herein, the term “haloalkyl” refers to C₁₋₁₀ alkyl groupssubstituted by one or more fluoro, chloro, bromo or iodo groups, e.g.,fluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl,1,1-difluoroethyl, chloromethyl, chlorofluoromethyl and trichloromethylgroups. The halo groups can be independently chosen.

As used herein, the term “halophenyl” refers to a phenyl groupsubstituted with one or more fluoro, chloro, bromo or iodo groups. Thehalo groups can be independently chosen, e.g., a di-halo substitutedphenyl can have a fluoro and a chloro substituent.

As used herein, the term “hydro” refers to an —H group.

As used herein, the term “hydroxyl” refers to an —OH group.

As used herein, the term “heteroaryl” refers to groups having 5 to 14ring atoms; 6, 10 or 14 π electrons shared in a cyclic array; andcontaining carbon atoms and 1, 2 or 3 oxygen, nitrogen or sulfurheteroatoms. Non-limiting heteroaryl groups include thienyl(thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl,furyl (furanyl), isobenzofuranyl, chromenyl, xanthenyl, phenoxanthiinyl,pyrrolyl, including without limitation 2H-pyrrolyl, imidazolyl,pyrazolyl, pyridyl (pyridinyl), including without limitation 2-pyridyl,3-pyridyl, and 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,indolizinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl,4H-quinolizinyl, isoquinolyl, quinolyl, phthalzinyl, naphthyridinyl,quinozalinyl, cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl,phenanthridinyl, acrindinyl, perimidinyl, phenanthrolinyl, phenazinyl,isothiazolyl, phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl,1,4-dihydroquinoxaline-2,3-dione, 7 aminoisocoumarin,pyrido[1,2-a]pyrimidin-4-one, pyrazolo[1,5-a]pyrimidinyl, includingwithout limitation pyrazolo[1,5-a]pyrimidin-3-yl,1,2-benzoisoxazol-3-yl, benzimidazolyl, 2-oxindolyl and 2oxobenzimidazolyl. Where the heteroaryl group contains a nitrogen atomin a ring, such nitrogen atom may be in the form of an N-oxide, e.g., apyridyl N oxide, pyrazinyl N-oxide and pyrimidinyl N-oxide. Heteroarylgroups can be monocyclic, bicyclic, tricyclic, and/or polycyclic.

As used herein, the term “heteroaryloxy” refers to oxygen substituted bya heteroaryl group as defined herein, which may be optionallysubstituted. Non-limiting heteroaryloxy groups include pyridyloxy,pyrazinyloxy, pyrrolyloxy, pyrazolyloxy, imidazolyloxy andthiophenyloxy.

As used herein, the term “heterocycle” or heterocyclic” refers to asaturated or partially saturated 3-7 membered monocyclic, 7-10 memberedbicyclic ring system, or 7-14 membered polycyclic ring system, whichcarbon atoms and from one to five heteroatoms independently selectedfrom the group consisting of O, N, and S, wherein the nitrogen andsulfur heteroatoms can be optionally oxidized, the nitrogen can beoptionally quaternized, and including any bicyclic group in which any ofthe above-defined heterocyclic rings is fused to a benzene ring, andwherein the heterocyclic ring can be substituted on carbon or on anitrogen atom if the resulting compound is stable (as is readilyrecognized by the skilled artisan). Non-limiting saturated or partiallysaturated heterocyclic groups include tetrahydrofuranyl, pyranyl,piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl,indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl,chromanyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl groups.

As used herein, the term “heteroarylalkoxy” refers to a C₁₋₁₀ alkoxygroups substituted by a heteroaryl group as defined herein, which may beoptionally substituted.

As used herein, the term “isocyanato” refers to a —NCO group.

As used herein, the term “isothiocyanato” refers to a —NCS group.

As used herein, the term “nitro” refers to a —NO₂ group.

As used herein, the term “sulfinyl” refers to a —S(═O)R″ group. R″ canbe a cycloalkyl or alkyl group. The alkyl or cycloalkyl group may beoptionally substituted.

As used herein, the term “sulfonyl” refers to a —S(═O)₂R″ group. R″ canbe a cycloalkyl or alkyl group. The alkyl or cycloalkyl group may beoptionally substituted.

As used herein, the term “sulfonamido” refers to a —S(═O)₂NR₁₇R₁₈.Independently, R₁₇ and R₁₈ may be hydro, C1-10 alkyl or cycloalkylgroups, or R₁₇ and R₁₈ are combined with the N to form a ring structure,such as a piperidine, or R₁₇ and R₁₈ are combined with the N and to forma ring, such as a piperazine. One of R₁₇ and R₁₈ can be hydro and theother alkyl or cycloalkyl. The alkyl or cycloalkyl group may beoptionally substituted.

As used herein, the term “thiocarbonyl” group refers to a —C(═S)R″group. R″ can be a cycloalkyl or alkyl group. The alkyl or cycloalkylgroup may be optionally substituted.

As used herein, the term “thiocyanato” refers to a —CNS group.

As used herein, the term “trihalomethanesulfonamido” refers to aX₃CS(═O)₂ NR₁₇-group with X being independently chosen from —Br, —Cl,—F, and —I groups and R₁₇ is as defined herein.

As used herein, the term “O-carbamyl” refers to a —OC(═O)NR₁₇R₁₈ group.R₁₇ and R₁₈ may be hydro, C₁₋₁₀ alkyl or cycloalkyl groups, or R₁₇ andR₁₈ are combined with the N to form a ring structure, such as apiperidine, or R₁₇ and R₁₈ are combined with the N and to form a ring,such as a piperazine. One of R₁₇ and R₁₈ can be hydro and the otheralkyl or cycloalkyl. The alkyl or cycloalkyl group may be optionallysubstituted.

As used herein, the term “N-carbamyl” refers to a R₁₈OC(═O)NR₁₇— group.R₁₈ may be hydro; R₁₇ and R₁₈ may be C1-10 alkyl or cycloalkyl groups,or R₁₇ and R₁₈ are combined with the N to form a ring structure, such asa piperidine, or R₁₇ and R₁₈ are combined with the N and to form a ring,such as a piperazine. One of R₁₇ and R₁₈ can be hydro and the otheralkyl or cycloalkyl. The alkyl or cycloalkyl group may be optionallysubstituted.

As used herein, the term “O-thiocarbamyl” refers to a —OC(═S)NR₁₇R₁₈group. R₁₇ and R₁₈ may be hydro, C₁₋₁₀ alkyl or cycloalkyl groups, orR₁₇ and R₁₈ are combined with the N to form a ring structure, such as apiperidine, or R₁₇ and R₁₈ are combined with the N and to form a ring,such as a piperazine. One of R₁₇ and R₁₈ can be hydro and the otheralkyl or cycloalkyl. The alkyl or cycloalkyl group may be optionallysubstituted.

As used herein, the term “N-thiocarbamyl” refers to a R₁₇OC(═S)NR₁₈—group. R₁₇ may be hydro; R₁₇ and R₁₈ may be C₁₋₁₀ alkyl or cycloalkylgroups. The alkyl or cycloalkyl group may be optionally substituted.

As used herein, the term “C-amido” refers to a —C(═O)NR₁₇R₁₈ group. An“N-amido” refers to a R₁₇C(═O)NR₁₈— group (R₁₈ is not hydro). R₁₇ andR₁₈ may be hydro, C1-10 alkyl or cycloalkyl groups, or R₁₇ and R₁₈ arecombined with the N to form a ring structure, such as a piperidine, orR₁₇ and R₁₈ are combined with the N and to form a ring, such as apiperazine. One of R₁₇ and R₁₈ can be hydro and the other alkyl orcycloalkyl. The alkyl or cycloalkyl group may be optionally substituted.

In some aspects, the alkyl, alkenyl, alkynyl, aryl, heteroaryl,cycloalkyl, carbocyclic and heterocyclic groups include one or morehalo, hydroxy, carboxyl, amino, nitro, cyano, C1-C6 acylamino, C1-C6acyloxy, C1-C6 alkoxy, aryloxy, alkylthio, C6-C10 aryl, C4-C7cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl(C2-C6)alkenyl,C6-C10 aryl(C2-C6)alkynyl, heterocyclic or heteroaryl groups, unlessotherwise specified.

In some aspects, the aryl, arylalkyl, arylalkenyl, arylalkynyl andheteroaryl and heteroarylalkyl groups can be optionally substituted withone or more halo, C1-C6 haloalkyl, C6-C10 aryl, C4-C7 cycloalkyl, C1-C6alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl(C1-C6)alkyl, C6-C10aryl(C2-C6)alkenyl, C6-C10 aryl(C2-C6)alkynyl, C1-C6 hydroxyalkyl,nitro, amino, ureido, cyano, C1-C6 acylamino, hydroxy, thiol, C1-C6acyloxy, azido, C1-C6 alkoxy, carboxy or C1-2 alkylenedioxy (e.g.,methylenedioxy) groups, unless otherwise specified.

2. Compounds and Compositions of the Invention

The invention relates to compounds of Formulae I-III. The invention alsorelates to pharmaceutical compositions having one or more compounds ofFormulae I-III and a pharmaceutically acceptable carrier (excipient).The compounds of Formulae I-III were discovered by the inventors to havepharmacological activity. One particular activity the compounds ofFormulae I-III were found to have is anticancer activity. The inventionrelates to compounds of Formulae I-III below. The invention also relatesto pharmaceutical compositions having one or more compounds of FormulaeI-III and a pharmaceutically acceptable excipient. The compounds ofFormulae I-III were discovered by the inventors to have pharmacologicalactivity. One particular activity the compounds of Formulae I-III werefound to have is anticancer activity. The invention relates to compoundsof Formulae I-III below. The invention also relates to pharmaceuticalcompositions having one or more compounds of Formulae I-III and apharmaceutically acceptable excipient. The compounds of Formulae I-IIIwere discovered by the inventors to have pharmacological activity. Oneparticular activity the compounds of Formulae I-III were found to haveis anticancer activity.

The invention provides compounds of Formula I wherein:

A is chosen from a substituted or unsubstituted aryl, heteroaryl,heterocyclic, or carbocyclic group;

B is chosen from a substituted or unsubstituted aryl, heteroaryl,heterocyclic, or carbocyclic group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl.

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)_(n)OC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—,—(CH₂)_(n)O(CH₂)_(n)—, —(CH₂)_(n)S(CH₂)_(n)—, and—(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n is independently chosen from0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon and/or nitrogencan be optionally substituted with one or more substituentsindependently chosen from hydroxyl, halo, alkoxy, alkyl, amino,cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl, aryl, cycloalkyl,and heterocyclic; wherein —R₂ and —R₃ are independently chosen from —H,alkyl, and —C(═O)OR₄; and wherein R₄ is an alkyl group (e.g., methyl,ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl).

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)_(n)OC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—,—(CH₂)_(n)O(CH₂)_(n)—, —(CH₂)_(n)S(CH₂)_(n)—, and—(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n is independently chosen from0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon and/or nitrogencan be optionally substituted with one or more substituentsindependently chosen from hydroxyl, halo, alkoxy, alkyl, amino,cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl, aryl, cycloalkyl,and heterocyclic; wherein —R₂ and —R₃ are independently chosen from —H,alkyl, and —C(═O)OR₄; and wherein R₄ is an alkyl group (e.g., methyl,ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl).

L₁ and L₂ can be in either orientation, e.g.,—(CH₂)_(n)NC(═S)S(CH₂)_(n)—, refers topurine-(CH₂)_(n)NC(═S)S(CH₂)_(n)-phenyl andpurine-(CH₂)_(n)SC(═S)N(CH₂)_(n)-phenyl orientations unless otherwisespecified.

According to one aspect, A is an aryl group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, —C≡N, —SO₃, and —COOH. In a more specificaspect of the invention, A is a phenyl group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, and —COOH. In an even more specificaspect, A is a phenyl group having one or more substituents chosen from—F, —Cl, —Br, —I, —OCH₃, —CF₃, —CH₃, —OCF₃, —C(═O)CH₃, —COOH, —C≡N, and—NO₂.

In one aspect of the compounds of the invention, A is an aryl group withone or more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂—In one specific aspect, A is aphenyl group.

In one aspect of the compounds of the invention, A is a phenyl grouphaving from 1-5 substituents independently chosen from acylamino,acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl,arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio,carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxyl,heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy, isocyanato,isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl,thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl,O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one aspect of the compounds of the invention, B is an arylgroup having one or more substituents chosen from halo, alkyl, alkoxy,haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, —SO₃, and —COOH. Inone specific aspect, B is a phenyl group. In a more specific aspect, Bis a phenyl group having one or more substituents chosen from halo,alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and—COOH. In an even more specific aspect, B is a phenyl group having oneor more substituents chosen from —F, —Cl, —Br, —I, —CH₃, —OCH₃, —CF₃,—OCF₃, —C(═O)CH₃, —COOH, —C≡N, and —NO₂

In one aspect of the compounds of the invention, B is an aryl group withone or more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, —SO₃, and —NO₂.

In one aspect of the compounds of the invention, B is a phenyl grouphaving from 1-5 substituents independently chosen from acylamino,acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl,arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio,carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxyl,heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy, isocyanato,isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl,thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl,O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzo[1,3]dioxole group. In one aspect of this embodiment, A is a6-bromo-benzo[1,3]dioxol-5-yl group. In one aspect of this embodiment, Ais an unsubstituted benzo[1,3]dioxole group. In one aspect of thisembodiment, A is a 6-iodo-benzo[1,3]dioxol-5-yl group. In one aspect ofthis embodiment, A is a 6-chloro-benzo[1,3]dioxol-5-yl group. In oneaspect of this embodiment, A is a 6-fluoro-benzo[1,3]dioxol-5-yl group.In one aspect of this embodiment, A has from 1-5 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedindanone group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstituted indanegroup. In one aspect of this embodiment, A has from 1-5 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzo[1,4]dioxane group. In one aspect of this embodiment, A has from1-5 substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzoxazinone group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzoxazine group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutedbenzodioxine group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstitutednaphthyl group. In one aspect of this embodiment, A has from 1-6substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.

According to one embodiment, A is a substituted or unsubstituted pyrrolegroup. In one aspect of this embodiment, A has from 1-3 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.According to one aspect A is unsubstituted.

According to one embodiment, A is a substituted or unsubstitutedpyridine group. In one aspect of this embodiment, A has from 1-4substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,A is unsubstituted.

According to one embodiment, A is a substituted or unsubstitutedcyclohexyl group. In one aspect of this embodiment, A has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,A is unsubstituted.

According to one embodiment, B is a substituted or unsubstitutedbenzo[1,3]dioxole group. In one aspect of this embodiment, B is a6-bromo-benzo[1,3]dioxol-5-yl group. In one aspect of this embodiment, Bis an unsubstituted benzo[1,3]dioxole group. In one aspect of thisembodiment, B is a 6-iodo-benzo[1,3]dioxol-5-yl group. In one aspect ofthis embodiment, B is a 6-chloro-benzo[1,3]dioxol-5-yl group. In oneaspect of this embodiment, B is a 6-fluoro-benzo[1,3]dioxol-5-yl group.In one aspect of this embodiment, B has from 1-4 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one embodiment, B is a substituted or unsubstitutednaphthyl group. In one aspect of this embodiment, B has from 1-6substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,B is unsubstituted.

According to one embodiment, B is a substituted or unsubstituted pyrrolegroup. In one aspect of this embodiment, B has from 1-3 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.According to one aspect of this embodiment, B is unsubstituted.

According to one embodiment, B is a substituted or unsubstitutedpyridine group. In one aspect of this embodiment, B has from 1-4substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,B is unsubstituted.

According to one embodiment, B is a substituted or unsubstitutedcyclohexyl group. In one aspect of this embodiment, B has from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido. According to one aspect of this embodiment,B is unsubstituted.

According to one aspect of the invention, compounds of Formula I areprovided wherein:

A is a substituted or unsubstituted aryl group;

B is a substituted or unsubstituted aryl group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl.

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)—, —(CH₂)_(n)C(═O)N(CH₂)—,—(CH₂)_(n)NC(═O)O(CH₂)—, —(CH₂)_(n)NC(═O)N(CH₂)—,—(CH₂)_(n)NC(═S)S(CH₂)_(n)—, —(CH₂)nOC(═O)S(CH₂)—, —(CH₂)_(n)NH(CH₂)—,—(CH₂)_(n)O(CH₂)—, —(CH₂)_(n)S(CH₂)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, whereeach n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, andwherein each carbon and/or nitrogen can be optionally substituted withone or more substituents independently chosen from hydroxyl, halo,alkoxy, C₁₋₃ alkyl, and C₃₋₆ cycloalkyl groups;

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)—, —(CH₂)_(n)C(═O)N(CH₂)—,—(CH₂)_(n)NC(═O)O(CH₂)—, —(CH₂)_(n)NC(═O)N(CH₂)—,—(CH₂)_(n)NC(═S)S(CH₂)_(n)—, —(CH₂)nOC(═O)S(CH₂)—, —(CH₂)_(n)NH(CH₂)—,—(CH₂)_(n)O(CH₂)—, —(CH₂)_(n)S(CH₂)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, whereeach n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, andwherein each carbon and/or nitrogen can be optionally substituted withone or more substituents independently chosen from hydroxyl, halo,alkoxy, C₁₋₃ alkyl, and C₃₋₆ cycloalkyl groups; and pharmaceuticallyacceptable salts thereof.

According to one aspect of the invention, compounds of Formula I areprovided wherein:

A is a substituted or unsubstituted heteroaryl group;

B is a substituted or unsubstituted aryl group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl;

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)—, —(CH₂)_(n)C(═O)N(CH₂)—,—(CH₂)_(n)NC(═O)O(CH₂)—, —(CH₂)_(n)NC(═O)N(CH₂)—,—(CH₂)_(n)NC(═S)S(CH₂)_(n)—, —(CH₂)nOC(═O)S(CH₂)—, —(CH₂)_(n)NH(CH₂)—,—(CH₂)_(n)O(CH₂)—, —(CH₂)_(n)S(CH₂)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, whereeach n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, andwherein each carbon and/or nitrogen can be optionally substituted withone or more substituents independently chosen from hydroxyl, halo,alkoxy, C₁₋₃ alkyl, and C₃₋₆ cycloalkyl groups;

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)—, —(CH₂)_(n)C(═O)N(CH₂)—,—(CH₂)_(n)NC(═O)O(CH₂)_(n)—, —(CH₂)_(n)NC(═O)N(CH₂)_(n)—,—(CH₂)NC(═S)S(CH₂)—, —(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—,—(CH₂)_(n)O(CH₂)_(n)—, —(CH₂)_(n)S(CH₂)_(n)—,—(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n is independently chosen from0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon and/or nitrogencan be optionally substituted with one or more substituentsindependently chosen from hydroxyl, halo, alkoxy, C₁₋₃ alkyl, and C₃₋₆cycloalkyl groups; and pharmaceutically acceptable salts thereof.

According to one aspect of the invention, compounds of Formula I areprovided wherein A is a substituted or unsubstituted aryl group; B is asubstituted or unsubstituted heteroaryl group; R1 is chosen from hydro,alkyl, aryl, heteroaryl, amino, halo, sulfur, and thioalkyl; andpharmaceutically acceptable salts thereof.

According to one aspect of the invention, compounds of Formula I areprovided wherein A is a substituted or unsubstituted heterocyclic group;B is a substituted or unsubstituted aryl group; and R1 is chosen fromhydro, alkyl, aryl, heteroaryl, alkyl amino, halo, sulfur, andthioalkyl.

According to one aspect of the invention, compounds of Formula I areprovided wherein A is a substituted or unsubstituted aryl group; B is asubstituted or unsubstituted heterocyclic group; R1 is chosen fromhydro, alkyl, aryl, heteroaryl, amino, halo, sulfur, and thioalkyl.

According to some aspects of the invention, in the compound of FormulaI, A is substituted or unsubstituted and chosen from indazolyl,1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzooxazolyl,1H-benzoimadazolyl, 3H-benzooxazol-2-one, 4H-benzo[1,4]oxazin-3-one, 1,3dihydro-benzoimadazol-2-one, 3H-benzothialo-2-one,1H-pyrazolo[3,4-b]pyridine, 1H-quinaxolin-2-one, 1H-quinaxolin-2-one,4H-benzo[1,4]oxazin-3-one, isoquinoline, indoline, 1,3dihydro-indol-2-one, 2,3-dihydro-benzo[1,4]dioxine, thienyl(thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl,furyl (furanyl), isobenzofuranyl, chromenyl, xanthenyl, phenoxanthiinyl,pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl),2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,indolizinyl, isoindolyl, 3H-indolyl, indolyl, purinyl, 4H-quinolizinyl,isoquinolyl, quinolyl, phthalzinyl, naphthyridinyl, quinozalinyl,cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl,acrindinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl,phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl,1,4-dihydroquinoxaline-2,3-dione, 7 aminoisocoumarin,pyrido[1,2-a]pyrimidin-4-one, pyrazolo[1,5-a]pyrimidinyl,pyrazolo[1,5-a]pyrimidin-3-yl, 1,2-benzoisoxazol-3-yl, benzimidazolyl,2-oxindolyl, 2 oxobenzimidazolyl, tetrahydrofuranyl, pyranyl,piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl,indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl,chromanyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

According to some aspects of the invention, in the compound of FormulaI, B is substituted or unsubstituted and chosen from indazolyl,1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzooxazolyl,1H-benzoimadazolyl, 3H-benzooxazol-2-one, 4H-benzo[1,4]oxazin-3-one, 1,3dihydro-benzoimadazol-2-one, 3H-benzothialo-2-one,1H-pyrazolo[3,4-b]pyridine, 1H-quinaxolin-2-one, 1H-quinaxolin-2-one,4H-benzo[1,4]oxazin-3-one, isoquinoline, indoline, 1,3dihydro-indol-2-one, 2,3-dihydro-benzo[1,4]dioxine, thienyl(thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl,furyl (furanyl), isobenzofuranyl, chromenyl, xanthenyl, phenoxanthiinyl,pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl),2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,indolizinyl, isoindolyl, 3H-indolyl, indolyl, purinyl, 4H-quinolizinyl,isoquinolyl, quinolyl, phthalzinyl, naphthyridinyl, quinozalinyl,cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl,acrindinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl,phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl,1,4-dihydroquinoxaline-2,3-dione, 7 aminoisocoumarin,pyrido[1,2-a]pyrimidin-4-one, pyrazolo[1,5-a]pyrimidinyl,pyrazolo[1,5-a]pyrimidin-3-yl, 1,2-benzoisoxazol-3-yl, benzimidazolyl,2-oxindolyl, 2 oxobenzimidazolyl, tetrahydrofuranyl, pyranyl,piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl,indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl,chromanyl, pyrazolidinyl, pyrazolinyl, tetronoyl, and tetramoyl.

In some aspects of the compounds of the invention, the A ring issubstituted with one or more substituents chosen from -L₁-C(═O)OH,-L₁-CH═CHC(═O)OH, -L₁-C(═O)NH₂, -L₁-C(═O)NH(C₁₋₃ alkyl), -L₁-C(═O)N(C₁₋₃alkyl)₂, -L₁-S(═O)₂(C₁₋₃alkyl), -L₁-S(═O)₂NH₂, -L₁-S(═O)₂N(C₁₋₃ alkyl)₂,-L₁-S(═O)₂NH(C₁₋₃ alkyl), -L₁-C(═O)NHOH, -L₁-C(═O)CH₂NH₂,-L₁-C(═O)CH₂OH, -L₁-C(═O)CH₂SH, -L₁-C(═O)NHCN, -L₁-NHC(═O)OR_(o),-L₁-C(═O)NHR_(o), -L₁-NH(C═O)NHR_(o), -L₁-C(═O)N(R_(o))₂,-L₁-NH(C═O)N(R_(o))₂, -L₁-sulfo; where R_(o) is chosen from alkyl andhaloalkyl, and L₁ is independent of any other L, in the compound and isdefined as above.

In some aspects of the compounds of the invention, the B ring issubstituted with one or more substituents chosen from -L₁-C(═O)OH,-L₁-CH═CHC(═O)OH, -L₁-C(═O)NH₂, -L₁-C(═O)NH(C₁₋₃ alkyl), -L₁-C(═O)N(C₁₋₃alkyl)₂, -L₁-S(═O)₂(C₁₋₃alkyl), -L₁-S(═O)₂NH₂, -L₁-S(═O)₂N(C₁₋₃ alkyl)₂,-L₁-S(═O)₂NH(C₁₋₃ alkyl), -L₁-C(═O)NHOH, -L₁-C(═O)CH₂NH₂,-L₁-C(═O)CH₂OH, -L₁-C(═O)CH₂SH, -L₁-C(═O)NHCN, -L₁-NHC(═O)OR_(o),-L₁-C(═O)NHR_(o), -L₁-NH(C═O)NHR_(o), -L₁-C(═O)N(R_(o))₂,-L₁-NH(C═O)N(R_(o))₂, -L₁-sulfo; where R_(o) is chosen from alkyl andhaloalkyl, and L₁ is independent of any other L, in the compound and isdefined as above.

According to one aspect of the compounds of the invention, L₁ is chosenfrom —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂, —CH(CH₃)CH₂—, —CH(CH₂CH₃)CH₂—,—CH(CH(CH₃)₂)CH₂—, —C(CH₂CH₂)CH₂—, —C(CH₂CH₂CH₂)CH₂—,—CH(CH(CH₃)CH₂CH₃)CH₂—, —CH(CH(CH₂)₄)CH₂—, —CH(CH(CH₂)₅)CH₂—,—CH(OH)CH₂—, and —CH(CH₂OH)CH₂—In a more specific aspect L₁ is chosenfrom —CH₂CH₂— and —CH₂CH₂CH₂—In an even more specific aspect, L₁ is—CH₂CH₂—. L₁ can be in either orientation, e.g., —CH(CH₂CH₂)CH₂— refersto purine-CH(CH₂CH₂)CH₂-phenyl and purine-CH₂CH(CH₂CH₂)-phenylorientations unless otherwise specified.

According to one aspect of the invention, compounds of Formula I areprovided where L₂ is chosen from —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂,—CH(CH₃)CH₂—, —CH(CH₂CH₃)CH₂—, —CH(CH(CH₃)₂)CH₂—, —C(CH₂CH₂)CH₂—,—C(CH₂CH₂CH₂)CH₂—, —CH(CH(CH₃)CH₂CH₃)CH₂—, —CH(CH(CH₂)₄)CH₂—,—CH(CH(CH₂)₅)CH₂—, —CH(OH)CH₂—, and —CH(CH₂OH)CH₂—. In a more specificaspect L₂ is chosen from —CH₂CH₂— and —CH₂CH₂CH₂—. In an even morespecific aspect L₂ is —CH₂CH₂—. L₂ can be in either orientation, e.g.,—CH(CH₂CH₂)CH₂-refers to e.g, purine-CH(CH₂CH₂)CH₂-phenyl andpurine-CH₂CH(CH₂CH₂)-phenyl orientations unless otherwise specified.

According to one aspect of the compounds of the invention, A is a groupchosen from 2,5-dimethoxyphenyl, 2,5-diethoxyphenyl,2,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-chlorophenyl, and4-benzonitrile. In this aspect, the positions (numbering) of thesubstituents are relative to the linkage of the phenyl group to thepurine core. In a specific embodiment of this aspect L₁ is —S—.

According to one aspect of the compounds of the invention, B is a groupchosen from 2-bromophenyl, 2-fluorophenyl, 2-chlorophenyl,3-fluorophenyl, 3-iodophenyl, 3-bromophenyl, 4-fluorophenyl,4-chlorophenyl, 4-bromophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl,2,6-dichlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl,4-chloro-2-fluorophenyl, 2-chloro-6-fluorophenyl, pentafluorophenyl,2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-benzoic acid,2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl,3-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl,3,4,5-trimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, p-tolyl, o-tolyl,2,5-dimethylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl,4-phenylethanone, 4-phenol, 4-benzenesulfonic acid,4-dimethylaminophenyl, 4-carbamic acid tert-butyl ester phenyl,4-aminophenyl, 3-trifluoromethoxyphenyl, and 3,5bistrifluoromethylphenyl. In this aspect, the positions (numbering) ofthe substituents are relative to the linkage of the phenyl group to thepurine core. In a specific embodiment of this aspect, L₂ is chosen from—CH₂—CH₂— and —CH₂—CH₂—CH₂—.

The invention also provides compounds of Formula II where the variablesare as in any of the above embodiments and aspects of the invention forthe compounds of Formula I.

The invention also provides compounds of Formula III where the variablesare as in any of the above embodiments and aspects of the invention forthe compounds of Formula I.

According to one aspect of the invention, compounds of Formula I areprovided wherein:

A is a substituted or unsubstituted heterocyclic group;

B is a substituted or unsubstituted aryl group;

R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, halo, sulfur,and thioalkyl;

L₁ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups;

L₂ can be saturated, partially saturated, or unsaturated, and is chosenfrom —(CH₂), —(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)nOC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—,—(CH₂)_(n)S(CH₂)_(n)—, —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n isindependently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and whereineach carbon and/or nitrogen can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy, C₁₋₃alkyl, and C₃₋₆ cycloalkyl groups; and pharmaceutically acceptable saltsthereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl or heterocyclic group;

B can be substituted or unsubstituted and is chosen from a heteroaryl orheterocyclic group having one or more hetero atoms chosen from —N—, —O—,—S—, and —P—;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In another aspect of the invention, A can be substituted orunsubstituted and is chosen from a benzo[1,3]dioxole or phenyl group;

B can be a substituted or unsubstituted heteroaryl or heterocyclic grouphaving one or more hetero atoms chosen from —N—, —O—, —S—, and —P—;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is a group chosen from 5-halo-benzo[1,3]dioxole (e.g,5-bromo-benzo[1,3]dioxole), dimethoxybenzene (e.g.,1,4-dimethoxybenzene, 2,3-dimethoxybenzene, and 2,4-dimethoxybenzene),and diethoxybenzene (e.g., 1,4-diethoxybenzene, 2,3-diethoxybenzene, and2,4-diethoxybenzene);

B can be substituted or unsubstituted and is chosen from a heteroaryl orheterocyclic group having one or more hetero atoms chosen from —N—, —O—,—S—, and —P—;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

B can be substituted or unsubstituted and is a heterocyclic group chosenfrom piperidine, pyrrolidine, azetidine, piperazine, morpholine, andtetrahydro-pyran;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are defined as above; and pharmaceutically acceptable saltsthereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

B is a group chosen from piperidine, piperidine-1-carboxylic acid ethylester, piperidine-1-carboxylic acid tert-butyl ester,2,2,6,6-tetramethyl-piperidine, piperidine-2,6-dione,piperidine-1-carbaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine,tetrahydro-pyran, adamantane, piperidine-1-carbaldehyde,1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine,1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine,piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylicacid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester,1-pyrrolidin-1-yl-ethanone, 1-methanesulfonyl-pyrrolidine,pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butylester, 1-methyl-azetidine, azetidine, azetidine-1-carbaldehyde,1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole,undecafluorocyclohexane, cyclohexyl-carbamic acid tert-butyl ester,1-piperazin-1-yl-ethanone, 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene,5-methyl 2,4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzylester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester,piperidine-1,2-dicarboxylic acid 1-tert butyl ester 2-ethyl ester,benzyl-1,2,3,6-tetrahydro-pyridine,hexahydro-4b-aza-cyclopropa[cd]pentalene,2-isopropyl-piperidine-1carboxylic acid tert-butyl ester,piperidine-1-carboxylic acid ethyl amide, piperidine-1-carboxylic acidisopropyl amide, piperidine-1-carboxylic acid tert-butyl amide,[{piperidine-1-carbonyl}amino]-acetic acid ethyl ester, isopropylpiperidine, isobutyl piperidine,2,2-dimethyl-1-piperidin-1-yl-propan-1-one,2,2-dimethyl-1-piperidin-1-yl-butan-1-one, 2-isopropyl-piperidine,1-isopropyl piperazine, and 1-cyclopentyl-piperazine.

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B can be substituted or unsubstituted and is a heteroaryl orheterocyclic group chosen from piperidine, pyrrolidine, azetidine,piperazine, morpholine, and tetrahydro-pyran.

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B is a group chosen from piperidine, piperidine-1-carboxylic acid ethylester, piperidine-1-carboxylic acid tert-butyl ester,2,2,6,6-tetramethyl-piperidine, piperidine-2,6-dione,piperidine-1-carbaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine,tetrahydro-pyran, adamantane, piperidine-1-carbaldehyde,1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine,1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine,piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylicacid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester,1-pyrrolidin-1-yl-ethanone, 1-methanesulfonyl-pyrrolidine,pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butylester, 1-methyl-azetidine, azetidine, azetidine-1-carbaldehyde,1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole,undecafluorocyclohexane, cyclohexyl-carbamic acid tert-butyl ester,1-piperazin-1-yl-ethanone, 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene,5-methyl 2,4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzylester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester,piperidine-1,2-dicarboxylic acid 1-tert butyl ester 2-ethyl ester,benzyl-1,2,3,6-tetrahydro-pyridine,hexahydro-4b-aza-cyclopropa[cd]pentalene,2-isopropyl-piperidine-1carboxylic acid tert-butyl ester,piperidine-1-carboxylic acid ethyl amide, piperidine-1-carboxylic acidisopropyl amide, piperidine-1-carboxylic acid tert-butyl amide,[{piperidine-1-carbonyl}amino]-acetic acid ethyl ester, isopropylpiperidine, isobutyl piperidine,2,2-dimethyl-1-piperidin-1-yl-propan-1-one,2,2-dimethyl-1-piperidin-1-yl-butan-1-one, 2-isopropyl-piperidine,1-isopropyl piperazine, and 1-cyclopentyl-piperazine;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A is a group chosen from5-halo-benzo[1,3]dioxole, dimethoxybenzene, and diethoxybenzene;

B is a group chosen from piperidine, piperidine-1-carboxylic acid ethylester, piperidine-1-carboxylic acid tert-butyl ester,2,2,6,6-tetramethyl-piperidine, piperidine-2,6-dione,piperidine-1-carbaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine,tetrahydro-pyran, adamantane, piperidine-1-carbaldehyde,1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine,1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine,piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylicacid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester,1-pyrrolidin-1-yl-ethanone, 1-methanesulfonyl-pyrrolidine,pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butylester, 1-methyl-azetidine, azetidine, azetidine-1-carbaldehyde,1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole,undecafluorocyclohexane, cyclohexyl-carbamic acid tert-butyl ester,1-piperazin-1-yl-ethanone, 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene,5-methyl 2,4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzylester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester,piperidine-1,2-dicarboxylic acid 1-tert butyl ester 2-ethyl ester,benzyl-1,2,3,6-tetrahydro-pyridine,hexahydro-4b-aza-cyclopropa[cd]pentalene,2-isopropyl-piperidine-1carboxylic acid tert-butyl ester,piperidine-1-carboxylic acid ethyl amide, piperidine-1-carboxylic acidisopropyl amide, piperidine-1-carboxylic acid tert-butyl amide,[{piperidine-1-carbonyl}amino]-acetic acid ethyl ester, isopropylpiperidine, isobutyl piperidine,2,2-dimethyl-1-piperidin-1-yl-propan-1-one,2,2-dimethyl-1-piperidin-1-yl-butan-1-one, 2-isopropyl-piperidine,1-isopropyl piperazine, and 1-cyclopentyl-piperazine;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

According to one aspect of the invention, in the compounds of Formula I,A is an aryl or heterocyclic group having one or more substituentschosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—C(═O)alkyl, hydroxyl, —C≡N, —SO₃, and —COOH. In a more specific aspectA is a phenyl group having one or more substituents chosen from halo,alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and—COOH. In another specific aspect, A is a phenyl group having one ormore substituents chosen from —F, —Cl, —Br, —I, —OCH₃, and —OCH₂CH₃. Inanother aspect A is a benzo[1,3]dioxole group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, and —COOH. In another specific aspect, Ais a benzo[1,3]dioxole group having one or more substituents chosen from—F, —Cl, —Br, —I, —OCH₃, and —OCH₂CH₃.

In one aspect, in the compounds of Formula I, A is an aryl orheterocyclic group with one or more substituents chosen from hydroxyl,halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂. In onespecific aspect, A is a phenyl group having one or more substituentschosen from hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl),—C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN,—NH₂, and —NO₂. In another specific aspect, A is a benzo[1,3]dioxolegroup having one or more substituents chosen from hydroxyl, halo, alkyl,alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl),—C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂.

In one aspect, in the compounds of Formula I, A is a phenyl orbenzo[1,3]dioxole group having from 1-5 substituents independentlychosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio,alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy,aryloxy, arylthio, carbocycle, cyano, cyanato, halo, haloalkyl,halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

According to one aspect, in the compounds of Formula I, B is aheterocyclic group having one or more heteroatoms chosen from —N— and—O— wherein the heterocyclic group can have one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), amino acid (chosen fromnatural and non-natural amino acids), peptide having 1-5 amino acidresidues (chosen from natural and non-natural amino acids), —C(═O)alkylwhere the alkyl is substituted with one or more substituents (chosenfrom alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano,hydroxyl, —COOH (and esters thereof), sulfonyl, sulfonamide) andsulfonyl. In one specific aspect, B is a piperidine (piperidinyl) group.In one specific aspect, B is a piperidine group substituted with one ormore substituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl. In a more specific aspect, B is apiperidine group having one or more substituents chosen from hydro,halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (andesters thereof), and sulfonyl. In an even more specific aspect, B is apiperidine group having one or more substituents chosen from —C(═O),—C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is a homopiperidine (homopiperidinyl) group.In a more specific aspect, B is a homopiperidine group having one ormore substituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl. In an even more specific aspect, Bis a homopiperidine group having one or more substituents chosen from—C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is a piperazine (piperazinyl) group. In a morespecific aspect, B is a piperazine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), amino acid (chosen fromnatural and non-natural amino acids), peptide having 1-5 amino acidresidues (chosen from natural and non-natural amino acids), —C(═O)alkylwhere the alkyl is substituted with one or more substituents (chosenfrom alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano,hydroxyl, —COOH (and esters thereof), sulfonyl, sulfonamide) andsulfonyl. In an even more specific aspect, B is a piperazine grouphaving one or more substituents chosen from —C(═O), —C(═O)CH₃, —CH₃,—CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃,—C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is a pyrrolidine (pyrrolidinyl) group. In amore specific aspect, B is a pyrrolidine group having one or moresubstituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O) cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl. In an even more specific aspect, Bis a pyrrolidine group having one or more substituents chosen from—C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one specific aspect, B is an azetidine (azetidinyl) group. In a morespecific aspect, B is an azetidine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), amino acid (chosen fromnatural and non-natural amino acids), peptide having 1-5 amino acidresidues (chosen from natural and non-natural amino acids), —C(═O)alkylwhere the alkyl is substituted with one or more substituents (chosenfrom alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano,hydroxyl, —COOH (and esters thereof), sulfonyl, sulfonamide) andsulfonyl. In an even more specific aspect, B is an azetidine grouphaving one or more substituents chosen from —C(═O), —C(═O)CH₃, —CH₃,—CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃,—C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one aspect of the compounds of Formula I, B is a heterocyclic groupwith one or more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, —SO₃, and —NO₂. In a specific aspect, Ba group is chosen piperidine, piperazine, pyrrolidine, azetidine,tetrahydro-pyran, and morpholine group, each having one or moresubstituents. In a more specific aspect, B is a piperidine group havingone or more substituents.

In one aspect, B is a group chosen from piperidine, piperazine,pyrrolidine, azetidine, tetrahydro-pyran, and morpholine, wherein said Bgroup can have from 1-5 substituents independently chosen fromacylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino,aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy,arylthio, carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl,hydroxyl, heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy,isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide,thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl,N-carbamyl, O-thio carbamyl, N-thiocarbamyl, and C-amido. In a morespecific aspect, B is a piperidine group having one or moresubstituents.

According to one embodiment, A is a substituted or unsubstitutedbenzo[1,3]dioxole group. In one aspect of this embodiment, A is a5-bromo-benzo[1,3]dioxole group. In one aspect of this embodiment, A isan unsubstituted benzo[1,3]dioxole group. In one aspect of thisembodiment, A is a 5-iodo-benzo[1,3]dioxole group. In one aspect of thisembodiment, A is a 5-chloro-benzo[1,3]dioxole group. In one aspect ofthis embodiment, A is a 5-fluoro-benzo[1,3]dioxole group. In one aspectof this embodiment, A has from 1-5 substituents independently chosenfrom acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl,amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy,arylthio, carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl,hydroxyl, heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy,isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide,thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl,N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

In one aspect of the invention, A is substituted with one or moresubstituents and is a group chosen from a phenyl or benzo[1,3]dioxolegroup; B is substituted with one or more substituents and is a groupchosen from piperidine, piperazine, pyrrolidine, azetidine,tetrahyro-pyran, and morpholine; R₁ is a hydro; L₁ is —S—; L₂ is—CH₂CH₂—, and pharmaceutically acceptable salt thereof. According tothis aspect of the invention, the A group substituents are chosen fromhalo and alkoxy, and the B group substituents are chosen from —C(═O),—C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl and heterocyclic group;

B can be substituted or unsubstituted and is chosen from a cycloalkyland heterocyclic group;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In another aspect of the invention, A can be substituted orunsubstituted and is chosen from a benzo[1,3]dioxole and phenyl group;

B can be substituted or unsubstituted and is chosen from a heteroaryl,heterocyclic, and cycloalkyl group;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is a group chosen from 5-halo-benzo[1,3]dioxole (e.g.,5-bromo-benzo[1,3]dioxole), dimethoxybenzene (e.g.,1,4-dimethoxybenzene, 2,3-dimethoxybenzene, and 2,4-dimethoxybenzene),and diethoxybenzene (e.g., 1,4-diethoxybenzene, 2,3-diethoxybenzene, and2,4-diethoxybenzene);

B can be substituted or unsubstituted and is chosen from a cycloalkyl,heteroaryl, and heterocyclic group;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

B can be substituted or unsubstituted and is a group chosen fromcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl,oxepanyl (oxepane), tetrahydro-thiophenyl (tetrahydro-thiophene),thiopyranyl, thiepanyl (thiepane), and tetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are defined as above; and pharmaceutically acceptable saltsthereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from an aryl, heteroaryl, heterocyclic, and carbocyclicgroup;

-L₂-B is a group chosen from (1-Cyclopropyl-propyl)-carbamic acidtert-butyl ester, [1-(Tetrahydro-thiopyran-4-yl)-propyl]-carbamic acidtert-butyl ester, (1-Cyclohexyl-propyl)-carbamic acid tert-butyl ester,(1-Cyclobutyl-propyl)-carbamic acid tert-butyl ester,N-(1-Cyclopropyl-propyl)-methanesulfonamide,1-(1-Cyclopropyl-propyl)-3-isopropyl-urea,(1-Cyclopentyl-propyl)-carbamic acid tert-butyl ester,[1-(Tetrahydro-pyran-4-yl)-propyl]-carbamic acid tert-butyl ester,1-Cyclopropyl-propylamine, 1-Cyclohexyl-propylamine,1-Cyclobutyl-propylamine, 1-Cyclopentyl-propylamine,1-(Tetrahydro-pyran-4-yl)-propylamine,1-(Tetrahydro-thiopyran-4-yl)-propyl amine, and1-(1-Cyclohexyl-propyl)-1H-pyrrole;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ is as defined above; and pharmaceutically acceptable salts thereof.

In some specific aspects of the invention, L₂ is as defined above andhas one or more substituents chosen from hydroxyl, halo, alkoxy, amino,C₁₋₃ alkyl, C₃₋₇ cycloalkyl, —N—C(═O)OC(CH₃)₃, —NSO₂CH₃,—NC(═O)NC(CH₃)₂, and pyrrolyl.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B can be substituted or unsubstituted and is a heteroaryl orheterocyclic group chosen from cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A can be substituted or unsubstitutedand is chosen from a benzo[1,3]dioxole and phenyl group;

B is a group chosen from cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

In one aspect of the invention, A is a group chosen from5-halo-benzo[1,3]dioxole, dimethoxybenzene, and diethoxybenzene;

B is a group chosen cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl;

R1 is chosen from a hydro, alkyl, alkoxy, aryl, heteroaryl,heterocyclic, carbocyclic, amino, halo, sulfur, and thioalkyl group;

L₁ and L₂ are as defined above in their broadest aspects; andpharmaceutically acceptable salts thereof.

According to one aspect of the invention, in the compounds of Formula I,A is an aryl or heterocyclic group having one or more substituentschosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—C(═O)alkyl, hydroxyl, —C≡N, —SO₃, and —COOH. In another specificaspect, A is a phenyl group having one or more substituents chosen fromhalo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl,hydroxyl, and —COOH. In another specific aspect, A is a phenyl grouphaving one or more substituents chosen from —F, —Cl, —Br, —I, —OCH₃, and—OCH₂CH₃. In another aspect, A is a benzo[1,3]dioxole group having oneor more substituents chosen from halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and —COOH. In another specificaspect, A is a benzo[1,3]dioxole group having one or more substituentschosen from —F, —Cl, —Br, —I, —OCH₃, and —OCH₂CH₃.

In one aspect, in the compounds of Formula I, A is an aryl orheterocyclic group with one or more substituents chosen from hydroxyl,halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂. In onespecific aspect, A is a phenyl group having one or more substituentschosen from hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl),—C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN,—NH₂, and —NO₂. In another specific aspect, A is a benzo[1,3]dioxolegroup having one or more substituents chosen from hydroxyl, halo, alkyl,alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl),—C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂

In one specific aspect of the compounds of the invention, B is acycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, or cycloheptyl)group. In another specific aspect, B is a cycloalkyl group having one ormore substituents chosen from hydro, halo, alkyl, alkoxy, haloalkyl,haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl,hydroxyl, —SO₃, —COOH (and esters thereof), and sulfonyl. In anotherspecific aspect, B is a cycloalkyl group having one or more substituentschosen from —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In one specific aspect of the compounds of the invention, B is athiopyranyl group. In another specific aspect, B is a thiopyranyl grouphaving one or more substituents chosen from hydro, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl,cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof), and sulfonyl. Inanother specific aspect, B is a thiopyranyl group having one or moresubstituents chosen from —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃,—C(═O)OCH₂CH₃, —S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃,—C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂, —C(═O)NHCH₂CH₃,—C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃, —C(═O)NHCH₂C(═O)OCH₂CH₃,—C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —C(═O)CH₂C(CH₃)₃, cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In one specific aspect of the compounds of the invention, B is atetrahydro-pyranyl group. In another specific aspect, B is atetrahydro-pyranyl group having one or more substituents chosen fromhydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (andesters thereof), and sulfonyl. In another specific aspect, B is atetrahydro-pyranyl group having one or more substituents chosen from—C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In one aspect, B is a group chosen cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydro-thiophenyl(tetrahydro-thiophene), thiopyranyl, thiepanyl (thiepane), andtetrahydro-pyranyl, wherein said B group can have from 1-5 substituentsindependently chosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl,alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl,arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo,haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

In one aspect of the invention, A is substituted with one or moresubstituents and is a group chosen from a phenyl or benzo[1,3]dioxolegroup; B is substituted with one or more substituents and is a groupchosen from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl,thiopyranyl, and tetrahydro-pyranyl; R₁ is a hydro; L₁ is —S—; L₂ is—CH₂CH₂—, and pharmaceutically acceptable salt thereof. According tothis aspect of the invention, the A group substituents are chosen fromhalo and alkoxy, and the B group substituents are chosen from —C(═O),—C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃, —S(═O)₂CH₃,—S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl, —CH(CH₃)₂,—C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In one aspect, the invention provides compounds of Formula I wherein R1is hydro.

In one aspect, the invention provides compounds of Formula I wherein L₁is —S—.

In one aspect, the invention provides compounds of Formula I whereinL₂-CH₂CH₂—.

In one aspect, the invention provides compounds of Formula I wherein L₂is —(CH₂), —(CH₂)_(n)—, and each n is independently chosen from 0, 1, 2,and 3 and wherein each carbon can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy,alkyl, amino, cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl,aryl, cycloalkyl, and heterocyclic; wherein —R₂ and —R₃ areindependently chosen from —H, alkyl, and —C(═O)OR₄; and wherein R₄ is analkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ortert-butyl).

Examples of compounds of the invention are in the Examples. In someaspects, compounds of the invention include those in the Examples thathave an IC50 of 10 μM or less. In some aspects, compounds of theinvention include those in the Examples that have an IC50 of 5 μM orless. In some aspects, compounds of the invention include those in theExamples that have an IC50 of 1 μM or less. In some aspects, compoundsof the invention include those in the Examples that have an IC50 of 0.5μM or less.

In some aspects, compounds of the invention include those in the as inany aspect of embodiment of the invention and that have an IC50 of 10 μMor less. In some aspects, compounds of the invention include those inthe as in any aspect of embodiment of the invention and that have anIC50 of 5 μM or less. In some aspects, compounds of the inventioninclude those in the as in any aspect of embodiment of the invention andthat have an IC50 of 1 μM or less. In some aspects, compounds of theinvention include those in the as in any aspect of embodiment of theinvention and that have an IC50 of 0.5 μM or less.

In some aspects, the inventions relates to compounds of the inventionare linked to a resins. In a specific aspect, the resin is chosen fromsephadex, tentagel and affigel.

As is understood by the skilled artisan, certain variables in the listof substituents are repetitive (different name for the samesubstituent), generic to other terms in the list, and/or partiallyoverlap in content with other terms. In the compounds of the invention,the skilled artisan recognizes that substituents may be attached to theremainder of the molecule via a number of positions and the preferredpositions are as illustrated in the Examples.

Additionally, the compounds of Formulae I-III can contain asymmetriccarbon atoms and can therefore exist in racemic and optically activeforms. Thus, optical isomers or enantiomers, racemates, tautomers, anddiastereomers are also encompassed in the compounds of Formulae I-III.The methods of present invention include the use of all such isomers andmixtures thereof. Methods of separation of enantiomeric anddiastereomeric mixtures are well known to one skilled in the art. Thepresent invention encompasses any isolated racemic or optically activeform of compounds described in Formulae I, or any mixture thereof.

In one embodiment, the invention provides a compound or a pharmaceuticalcomposition comprising the compound where the compound chosen from8-(2,5-dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(2,4-dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,4-dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(4-chloro-phenylsulfonyl)-9-phenethyl-9H-purin-6-ylamine,8-(4-chloro-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,4-(6-amino-9-phenethyl-9H-purin-8-ylsulfanyl)-b enzonitrile,4-(6-amino-3-phenethyl-3H-purin-8-ylsulfanyl)-benzonitrile,9-[2-(3,4-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(3,4-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine,9-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2,4-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2,4-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenyl-sulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,9-[2-(4-chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(4-chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(-6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-chloro-2-fluorophenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pentafluorophenyl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-phenyl-propyl)-3H-purin-6-ylamine,9-phenethyl-8-(3,4,5-trimethoxy-phensulfanyl)-9H-purin-6-ylamine,3-phenethyl-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(3-phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine.3-(3-phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-pyrrol-1-yl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-pyrrol-1-yl-propyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-chloro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-phenyl-butyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-3H-purin-6-ylamine,9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone,1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine,9-[2-(4-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(4-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2,3-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2,3-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzoicacid,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzoicacid,8-(2,5-dimethoxy-phenylsulfanyl)-3-(4-fluoro-benzyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(4-nitro-benzyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-phenyl)-butyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-3H-purin-6-ylamine,9-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclopentyl-2-phenyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-cyclopentyl-2-phenyl-ethyl)-3H-purin-6-ylamine,9-(2-cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine,2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)ethanol,2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)ethanol,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,9-[2-(4-Chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,3-[2-(4-chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine,9-[2-(2,4-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,3-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3,5-dimethyl-phenyl)-ethyl]-9H-purine-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,5-dimethyl-phenyl)-ethyl]-3H-purine-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyridin-4-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyridin-2-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-pyridin-2-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine,9-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(6-Bromo-1,3-benzodioxol-5-ylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-bromo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-bromo-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyridin-3-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyridin-3-yl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine,1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone,1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,3-difluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-1,3-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,3-difluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine,9-(2-benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxyphenyl-sulfanyl)-9H-purin-6-ylamine,3-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,3-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3H-purin-6-ylamine,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzenesulfonicacid,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzenesulfonicacid,2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)-ethanol,2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)-ethanol,9-(2-Cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-cyclohexyl-2-phenyl-ethyl)-8-(25-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-diethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,5-diethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,9-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,5-dimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,5-dimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylmethyl)-9-phenethyl-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylmethyl)-3-phenethyl-3H-purin-6-ylamine,(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester,(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester,9-[2-(4-amino-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester,(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester,9-[2-(4-amino-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine,9-[2-(3,5-bistrifluoromethyl-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(3,5-Bistrifluoromethyl-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-nitro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one,and8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one.

In one embodiment, the invention provides a compound or a pharmaceuticalcomposition comprising the compound where the compound is chosen from8-(2,5-dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,4-dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(4-chloro-phenylsulfonyl)-9-phenethyl-9H-purin-6-ylamine,4-(6-amino-9-phenethyl-9H-purin-8-ylsulfanyl)-benzonitrile9-[2-(3,4-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine9-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(2,4-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,9-[2-(4-chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(-6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-chloro-2-fluorophenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,9-phenethyl-8-(3,4,5-trimethoxy-phensulfanyl)-9H-purin-6-ylamine,9-(3-phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-pyrrol-1-yl-propyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine,9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone,1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine,9-[2-(4-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(2,3-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzoicacid,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzoicacid,8-(2,5-dimethoxy-phenylsulfanyl)-9-(4-nitro-benzyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-9H-purin-6-ylamine,9-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclopentyl-2-phenyl-ethyl)-9H-purin-6-ylamine,9-(2-cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)ethanol,2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)ethanol,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,9-[2-(4-Chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,9-[2-(2,4-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3,5-dimethyl-phenyl)-ethyl]-9H-purine-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyridin-4-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyridin-2-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine,9-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(2-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(6-Bromo-1,3-benzodioxol-5-ylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-bromo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyridin-3-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine,1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone,1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,3-difluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,9-(2-benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxyphenyl-sulfanyl)-9H-purin-6-ylamine,9-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzenesulfonicacid,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzenesulfonicacid,2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)-ethanol,2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)-ethanol,9-(2-Cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-diethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,9-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,5-dimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylmethyl)-9-phenethyl-9H-purin-6-ylamine,(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester,(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester,9-[2-(4-amino-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester,(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester,9-[2-(4-amino-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine,9-[2-(3,5-bistrifluoromethyl-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(3,5-Bistrifluoromethyl-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one,and8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one.

In one aspect, the invention also provides compounds of Formula I and IIwherein said compound is chosen from the group consisting of2-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-piperidine-1-carboxylicacid ethyl ester;2-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-piperidine-1-carboxylicacid ethyl ester; Ethyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;Ethyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;tert-Butyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl4-(2-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl4-(2-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;tert-Butyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;tert-Butyl3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;tert-Butyl3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl3-(2-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-9H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-3-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(2,2,6,6-tetramethylpiperidin-4-y)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1-methylpyrrolidin-2-yl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(-methylpyrrolidin-2-yl)ethyl]-9H-purin-6-amine;9-[2-(1-Adamantyl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;3-[2-(1-Adamantyl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine;4-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde;4-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde;8-[(2,5-Dimethoxyphenyl)thio]-3-[2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-9H-purin-6-amine;tert-Butyl4-(2-{6-amino-8-[(2,5-diethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde;9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(methylsulfonyl)piperidin-4-yl]ethyl}-3H-purin-6-amine;tert-Butyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)morpholine-4-carboxylate;tert-Butyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)morpholine-4-carboxylate;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(methylsulfonyl)piperidin-3-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(methylsulfonyl)piperidin-3-yl]ethyl}-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-{2-[1-(methylsulfonyl)piperidin-2-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(methylsulfonyl)piperidin-2-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(methylsulfonyl)piperidin-2-yl]ethyl}-3H-purin-6-amine;9-(2-Cycloheptylethyl)-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(undecafluorocyclohexyl)ethyl]-9H-purin-6-amine;3-(2-Cycloheptylethyl)-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(undecafluorocyclohexyl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(methylsulfonyl)piperidin-4-yl]ethyl}-9H-purin-6-amine;8-(1,3-Benzodioxol-5-ylthio)-9-{2-[1-(methylsulfonyl)piperidin-4-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1H-imidazol-1-yl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1H-imidazol-1-yl)ethyl]-9H-purin-6-amine;9-[2-(4-Acetylpiperazin-1-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;3-[2-(4-Acetylpiperazin-1-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(undecafluorocyclohexyl)ethyl]-9H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-3-[2-(undecafluorocyclohexyl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-propylpiperidin-2-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-{1-[(trifluoromethyl)sulfonyl]piperidin-4-yl}methyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2-{1-[(trifluoromethyl)sulfonyl]piperidin-4-yl}ethyl)-3H-purin-6-amine;tert-Butyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethylidene)piperidine-1-carboxylate;tert-Butyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethylidene)piperidine-1-carboxylate;tert-Butyl(3S)-3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl(3R)-3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl(3R)-3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;tert-Butyl(2R)-2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl(2R)-2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-{1-[(trifluoromethyl)sulfonyl]piperidin-2-yl}ethyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2-{1-[(trifluoromethyl)sulfonyl]piperidin-2-yl}ethyl)-3H-purin-6-amine;tert-Butyl[cis-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)cyclohexyl]carbamate;tert-Butyl[cis-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)cyclohexyl]carbamate;9-[2-(1-Acetylpiperidin-3-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;3-[2-(1-Acetylpiperidin-3-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-{1-[(trifluoromethyl)sulfonyl]piperidin-3-yl}ethyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2-{1-[(trifluoromethyl)sulfonyl]piperidin-3-yl}ethyl)-3H-purin-6-amine;8-[(6-Bromo1,3-benzodioxal-5-yl)thio]-3-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-3-yl)ethyl]-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-3-yl)ethyl]-9H-purin-6-amine;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one;4-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one;4-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-3-yl}ethyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one;Benzyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;Benzyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-morpholin-4-ylethyl)-9H-purin-6-amine;tert-Butyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)pyrrolidine-1-carboxylate;tert-Butyl3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)pyrrolidine-1-carboxylate;tert-Butyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)pyrrolidine-1-carboxylate;tert-Butyl3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)pyrrolidine-1-carboxylate;tert-Butyl(2S)-2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate;tert-Butyl(2S)-2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate;tert-Butyl(3R)-3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)pyrrolidine-1-carboxylate;Benzyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)pyrrolidine-1-carboxylate;tert-Butyl(3S)-3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)pyrrolidine-1-carboxylate;Benzyl2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)pyrrolidine-1-carboxylate;1-tert-Butyl 2-ethyl(2S,4S)-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1,2-dicarboxylate;1-tert-Butyl 2-ethyl(2S,4R)-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1,2-dicarboxylate;9-[2-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;3-[2-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]ethyl}-3H-purin-6-amine;tert-Butyl(2R,4S)-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-2-isopropylpiperidine-1-carboxylate;tert-Butyl(2S,4S)-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-2-isopropylpiperidine-1-carboxylate;tert-Butyl(2S,4R)-4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-2-isopropylpiperidine-1-carboxylate;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N-ethylpiperidine-1-carboxamide;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N-isopropylpiperidine-1-carboxamide;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N-(tert-butyl)piperidine-1-carboxamide;EthylN-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}glycinate;3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N-ethylpiperidine-1-carboxamide;3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N-isopropylpiperidine-1-carboxamide;3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N-(tert-butyl)piperidine-1-carboxamide;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-N-ethylpiperidine-1-carboxamide;4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-N-isopropylpiperidine-1-carboxamide;3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-N-ethylpiperidine-1-carboxamide;3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-N-isopropylpiperidine-1-carboxamide;3-(2-{1-6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-N-(tert-butyl)piperidine-1-carboxamide;EthylN-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]carbonyl}glycinate;8-[(2,5-Dimethoxyphenyl)thio]-9-{2-[4-(2,2-dimethylpropanoyl)piperazin-1-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-isopropylpiperidin-2-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(-isopropylpiperidin-2-yl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-isobutylpiperidin-2-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1-isobutylpiperidin-2-yl)ethyl]-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(2,2-dimethylpropanoyl)piperidin-3-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(2,2-dimethylpropanoyl)piperidin-3-yl]ethyl}-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]ethyl}-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-isobutylpiperidin-4-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(3,3-dimethylbutanoyl)piperidin-3-yl]ethyl}-9H-purin-6-amine;8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-4-ylethyl)-9H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-3-(2-piperidin-4-ylethyl)-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2-piperidin-4-ylethyl)-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-(2-piperidin-4-ylethyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-3-yl}ethyl)-9H-purin-6-amine;8-[(2,5-dimethoxyphenyl)thio]-9-(2-piperidin-3-ylethyl)-9H-purin-6-amine;8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-4-ylideneethyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(3R)-piperidin-3-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(3S)-piperidin-3-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(2R)-piperidin-2-yl]ethyl}-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-pyrrolidin-3-ylethyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(2S)-piperidin-2-yl]ethyl}-9H-purin-6-amine;8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-2-[(3R)-pyrrolidin-3-yl]ethyl}-9H-purin-6-amine;8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(2R,4S)-2-isopropylpiperidin-4-yl]ethyl}-9H-purin-6-amine;8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[(2S)-2-isopropylpiperidin-4-yl]ethyl}-9H-purin-6-amine;8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-piperidine-1-yl-ethyl)-9H-purin-6-ylamine;8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-piperidine-1-yl-ethyl)-3H-purin-6-ylamine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(4-isopropylpiperazin-1-yl)ethyl]-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(4-isopropylpiperazin-1-yl)ethyl]-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-(2-piperidin-1-ylethyl)-9H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-3-(2-piperidin-1-ylethyl)-3H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-1-ylethyl)-9H-purin-6-amine;8-[(6-Bromo-1,3-benzodioxo-5-yl)thio]-5-yl)thio]-3-(2-piperidin-1-ylethyl)-3H-purin-6-amine;8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(4-isopropylpiperazin-1-yl)ethyl]-9H-purin-6-amine;9-[2-(4-Cyclopentylpiperazin-1-yl)ethyl]-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-6-amine;3-[2-(4-Cyclopentylpiperazin-1-yl)ethyl]-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-6-amine;1-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-2,6-dione;1-(2-{6-amino-8[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-2,6-dione;and a pharmaceutically acceptable salt thereof.

In one aspect, the invention also provides compounds of Formula I and IIwherein said compound is chosen from tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)carbamate;tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)carbamate;tert-Butyl(3-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)carbamate;tert-Butyl(3-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)carbamate;tert-Butyl[3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-(tetrahydro-2H-thiopyran-4-yl)propyl]carbamate;tert-Butyl[3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-(tetrahydro-2H-thiopyran-4-yl)propyl]carbamate;tert-Butyl[3-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}-1-(tetrahydro-2H-thiopyran-4-yl)propyl]carbamate;tert-Butyl[3-{6-amino-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-3-yl}-1-(tetrahydro-2H-thiopyran-4-yl)propyl]carbamate;tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclohexylpropyl)carbamate;tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclohexylpropyl)carbamate;tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclobutylpropyl)carbamate;tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclobutylpropyl)carbamate;N-(3-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)methanesulfonamide;N-(3-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)methanesulfonamide;N-3-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)methanesulfonamide;N-(3-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)methanesulfonamide;N-(3-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)-N′-isopropylurea;N-(3-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)-N′-isopropylurea;{3-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-cyclopentyl-propyl}-carbamicacid tert-butyl ester;{3-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-cyclopentyl-propyl}-carbamicacid tert-butyl ester;[3-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(tetrahydro-pyran-4-yl)-propyl]-carbamicacid tert-butyl ester;[3-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-3-yl]-1-(tetrahydro-pyran-4-yl)-propyl]-carbamicacid tert-butyl ester;[3-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-3-yl]-1-(tetrahydro-pyran-4-yl)-propyl]-carbamicacid tert-butyl ester;8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[3-cyclohexyl-3-(1H-pyrrol-1-yl)propyl]-3H-purin-6-amine;9-(3-amino-3-cyclobutylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;9-(3-Amino-3-cyclopropylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;3-(3-Amino-3-cyclopropylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine;9-[3-Amino-3-(tetrahydro-2H-thiopyran-4-yl)propyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;9-(3-Amino-3-cyclohexylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine;9-(3-Amino-3-cyclopentyl-propyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine;9-[3-Amino-3-(tetrahydro-pyran-4-yl)-propyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine;and a pharmaceutically acceptable salt thereof.

In another aspect, the invention is directed to pharmaceuticalcompositions comprising the compounds of the invention, in particular,one or more compounds of Formula I-III and one or more pharmaceuticalexcipients, for use in treatment or prevention of diseases that areHSP90-dependent.

In another aspect, the invention features a method of treating anindividual having an HSP90-mediated disorder by administering to theindividual a pharmaceutical composition that comprises apharmaceutically effective amount of one or more compounds of FormulaeI-III and/or a pharmaceutically acceptable salt thereof.

In one aspect, the invention provides a method for treating anindividual having a disorder chosen from inflammatory diseases,infections, autoimmune disorders, stroke, ischemia, cardiac disorders,neurological disorders, fibrogenetic disorders, proliferative disorders,tumors, leukemias, neoplasms, cancers, carcinomas, metabolic diseases,and malignant disease. In a specific aspect, the method involvesidentifying a patient in need of treatment and administering to

In yet another aspect, the invention provides a method for treating anindividual having a fibrogenetic disorder, such as, for example,scleroderma, polymyositis, systemic lupus, rheumatoid arthritis, livercirrhosis, keloid formation, interstitial nephritis and pulmonaryfibrosis.

The present invention also includes a therapeutic method comprisingadministering to an animal (e.g., a patient, in need of treatment) atherapeutically effective amount of one or more compounds of FormulaeI-III and/or a pharmaceutically acceptable salt thereof. The therapeuticmethod is useful to treat cancer, which is a group of diseasescharacterized by the uncontrolled growth and spread of abnormal cells.Such diseases include, but are not limited to, Hodgkin's disease,non-Hodgkin's lymphoma, acute lymphocytic leukemia, chronic lymphocyticleukemia, multiple myeloma, neuroblastoma, breast carcinoma, ovariancarcinoma, lung carcinoma, Wilms' tumor, cervical carcinoma, testicularcarcinoma, soft-tissue sarcoma, primary macroglobulinemia, bladdercarcinoma, chronic granulocytic leukemia, primary brain carcinoma,malignant melanoma, small-cell lung carcinoma, stomach carcinoma, coloncarcinoma, malignant pancreatic insulinoma, malignant carcinoidcarcinoma, choriocarcinoma, mycosis fungoides, head or neck carcinoma,osteogenic sarcoma, pancreatic carcinoma, acute granulocytic leukemia,hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma,genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma,malignant hypercalcemia, cervical hyperplasia, renal cell carcinoma,endometrial carcinoma, polycythemia vera, essential thrombocytosis,adrenal cortex carcinoma, skin cancer, and prostatic carcinoma.

Typically, compounds according to Formulae I-III can be effective at anamount of from about 0.01 μg/kg to about 100 mg/kg per day based ontotal body weight. The active ingredient may be administered at once, ormay be divided into a number of smaller doses to be administered atpredetermined intervals of time. The suitable dosage unit for eachadministration can be, e.g., from about 1 μg to about 2000 mg,preferably from about 5 μg to about 1000 mg.

It should be understood that the dosage ranges set forth above areexemplary only and are not intended to limit the scope of thisinvention. The therapeutically effective amount for each active compoundcan vary with factors including but not limited to the activity of thecompound used, stability of the active compound in the patient's body,the severity of the conditions to be alleviated, the total weight of thepatient treated, the route of administration, the ease of absorption,distribution, and excretion of the active compound by the body, the ageand sensitivity of the patient to be treated, and the like, as will beapparent to a skilled artisan. The amount of administration can beadjusted as the various factors change over time.

In the pharmaceutical compositions, the active agents can be in anypharmaceutically acceptable salt form. As used herein, the term“pharmaceutically acceptable salts” refers to the relatively non-toxic,organic or inorganic salts of the active compounds, including inorganicor organic acid addition salts of the compound. Examples of salts ofbasic active ingredient compounds include, but are not limited to,hydrochloride salts, hydrobromide salts, sulfate salts, bisulfate salts,nitrate salts, acetate salts, phosphate salts, nitrate salts, oxalatesalts, valerate salts, oleate salts, borate salts, benzoate salts,laurate salts, stearate salts, palmitate salts, lactate salts, tosylatesalts, citrate salts, maleate salts, succinate salts, tartrate salts,napththylate salts, fumarate salts, mesylate salts, laurylsuphonatesalts, glucoheptonate salts, and the like. See, e.g., Berge, et al. J.Pharm. Sci., 66:1-19 (1977). Examples of salts of acidic activeingredient compounds include, e.g., alkali metal salts, alkaline earthsalts, and ammonium salts. Thus, suitable salts may be salts ofaluminum, calcium, lithium, magnesium, potassium, sodium and zinc. Inaddition, organic salts may also be used including, e.g., salts oflysine, N,N′-dibenzylethylenediamine, chloroprocaine, choline,diethanolamine, ethylenediamine, meglumine (N-methylglucamine), procaineand tris.

For oral delivery, the active compounds can be incorporated into aformulation that includes pharmaceutically acceptable carriers such asbinders (e.g., gelatin, cellulose, gum tragacanth), excipients (e.g.,starch, lactose), lubricants (e.g., magnesium stearate, silicondioxide), disintegrating agents (e.g., alginate, Primogel, and cornstarch), and sweetening or flavoring agents (e.g., glucose, sucrose,saccharin, methyl salicylate, and peppermint). The formulation can beorally delivered in the form of enclosed gelatin capsules or compressedtablets. Capsules and tablets can be prepared in any conventionaltechniques. The capsules and tablets can also be coated with variouscoatings known in the art to modify the flavors, tastes, colors, andshapes of the capsules and tablets. In addition, liquid carriers such asfatty oil can also be included in capsules.

Suitable oral formulations can also be in the form of suspension, syrup,chewing gum, wafer, elixir, and the like. If desired, conventionalagents for modifying flavors, tastes, colors, and shapes of the specialforms can also be included. In addition, for convenient administrationby enteral feeding tube in patients unable to swallow, the activecompounds can be dissolved in an acceptable lipophilic vegetable oilvehicle such as olive oil, corn oil and safflower oil.

The active compounds can also be administered parenterally in the formof solution or suspension, or in lyophilized form capable of conversioninto a solution or suspension form before use. In such formulations,diluents or pharmaceutically acceptable carriers such as sterile waterand physiological saline buffer can be used. Other conventionalsolvents, pH buffers, stabilizers, anti-bacteria agents, surfactants,and antioxidants can all be included. For example, useful componentsinclude sodium chloride, acetates, citrates or phosphates buffers,glycerin, dextrose, fixed oils, methyl parabens, polyethylene glycol,propylene glycol, sodium bisulfate, benzyl alcohol, ascorbic acid, andthe like. The parenteral formulations can be stored in any conventionalcontainers such as vials and ampoules.

Routes of topical administration include nasal, bucal, mucosal, rectal,or vaginal applications. For topical administration, the activecompounds can be formulated into lotions, creams, ointments, gels,powders, pastes, sprays, suspensions, drops and aerosols. Thus, one ormore thickening agents, humectants, and stabilizing agents can beincluded in the formulations. Examples of such agents include, but arenot limited to, polyethylene glycol, sorbitol, xanthan gum, petrolatum,beeswax, or mineral oil, lanolin, squalene, and the like. A special formof topical administration is delivery by a transdermal patch. Methodsfor preparing transdermal patches are disclosed, e.g., in Brown, et al.,Annual Review of Medicine, 39:221-229 (1988), which is incorporatedherein by reference.

Subcutaneous implantation for sustained release of the active compoundsmay also be a suitable route of administration. This entails surgicalprocedures for implanting an active compound in any suitable formulationinto a subcutaneous space, e.g., beneath the anterior abdominal wall.See, e.g., Wilson et al., J. Clin. Psych. 45:242-247 (1984). Hydrogelscan be used as a carrier for the sustained release of the activecompounds. Hydrogels are generally known in the art. They are typicallymade by crosslinking high molecular weight biocompatible polymers into anetwork, which swells in water to form a gel like material. Preferably,hydrogels are biodegradable or biosorbable. For purposes of thisinvention, hydrogels made of polyethylene glycols, collagen, orpoly(glycolic-co-L-lactic acid) may be useful. See, e.g., Phillips etal., J. Pharmaceut. Sci., 73:1718-1720 (1984).

The active compounds can also be conjugated, to a water solublenon-immunogenic non-peptidic high molecular weight polymer to form apolymer conjugate. For example, an active compound is covalently linkedto polyethylene glycol to form a conjugate. Typically, such a conjugateexhibits improved solubility, stability, and reduced toxicity andimmunogenicity. Thus, when administered to a patient, the activecompound in the conjugate can have a longer half-life in the body, andexhibit better efficacy. See generally, Burnham, Am. J. Hosp. Pharm.,15:210-218 (1994). PEGylated proteins are currently being used inprotein replacement therapies and for other therapeutic uses. Forexample, PEGylated interferon (PEG-INTRON A®) is clinically used fortreating Hepatitis B. PEGylated adenosine deaminase (ADAGEN®) is beingused to treat severe combined immunodeficiency disease (SCIDS).PEGylated L-asparaginase (ONCAPSPAR®) is being used to treat acutelymphoblastic leukemia (ALL). It is preferred that the covalent linkagebetween the polymer and the active compound and/or the polymer itself ishydrolytically degradable under physiological conditions. Suchconjugates known as “prodrugs” can readily release the active compoundinside the body. Controlled release of an active compound can also beachieved by incorporating the active ingredient into microcapsules,nanocapsules, or hydrogels generally known in the art. Otherpharmaceutically acceptable prodrugs of the compounds of this inventioninclude, but are not limited to, esters, carbonates, thiocarbonates,N-acyl derivatives, N-acyloxyalkyl derivatives, quaternary derivativesof tertiary amines, N-Mannich bases, Schiff bases, aminoacid conjugates,phosphate esters, metal salts and sulfonate esters.

Liposomes can also be used as carriers for the active compounds of thepresent invention. Liposomes are micelles made of various lipids such ascholesterol, phospholipids, fatty acids, and derivatives thereof.Various modified lipids can also be used. Liposomes can reduce thetoxicity of the active compounds, and increase their stability. Methodsfor preparing liposomal suspensions containing active ingredientstherein are generally known in the art. See, e.g., U.S. Pat. No.4,522,811; Prescott, Ed., Methods in Cell Biology, Volume XIV, AcademicPress, New York, N.Y. (1976).

The active compounds can also be administered in combination withanother active agent that synergistically treats or prevents the samesymptoms or is effective for another disease or symptom in the patienttreated so long as the other active agent does not interfere with oradversely affect the effects of the active compounds of this invention.Such other active agents include but are not limited toanti-inflammation agents, antiviral agents, antibiotics, antifungalagents, antithrombotic agents, cardiovascular drugs, cholesterollowering agents, anti-cancer drugs, hypertension drugs, and the like.

Examples of antineoplastic agents that can be used in combination withthe compounds and methods of the present invention include, in general,and as appropriate, alkylating agents, anti-metabolites,epidophyllotoxins, antineoplastic enzymes, topoisomerase inhibitors,procarbazines, mitoxantrones, platinum coordination complexes,biological response modifiers and growth inhibitors,hormonal/anti-hormonal therapeutic agents and haematopoietic growthfactors. Exemplary classes of antineoplastic include the anthracyclines,vinca drugs, mitomycins, bleomycins, cytotoxic nucleosides, epothilones,discodermolides, pteridines, diynenes and podophyllotoxins. Particularlyuseful members of those classes include, for example, caminomycin,daunorubicin, aminopterin, methotrexate, methopterin,dichloromethotrexate, mitomycin C, porfiromycin, 5-fluorouracil,6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin orpodo-phyllotoxin derivatives such as etoposide, etoposide phosphate orteniposide, melphalan, vinblastine, vincristine, leurosidine, vindesine,leurosine, paclitaxel and the like. Other useful antineoplastic agentsinclude estramustine, carboplatin, cyclophosphamide, bleomycin,gemcitibine, ifosamide, melphalan, hexamethyl melamine, thiotepa,cytarabin, idatrexate, trimetrexate, dacarbazine, L-asparaginase,camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide,leuprolide, pyridobenzoindole derivatives, interferons and interleukins.

EXAMPLES

Chemicals were purchased from standard commercial vendors and used asreceived unless otherwise noted. Otherwise their preparation is facileand known to one of ordinary skill in the art, or it is referenced ordescribed herein.

Abbreviations are consistent with those in the ACS Style Guide. “dry”glassware means oven/desiccator dried. Solvents were ACS grade unlessotherwise noted. Analytical TLC plates (Silica Gel 60 F254, EM Science,Gibbstown, N.J., or Merck # 5715) were used to follow the course ofreactions, and the MPLC system used for purifications was from Isco(Foxy Jr fraction collector, UA-6 detector), using Isco silica gel flashcolumns (10 or 40 g). ¹H NMR spectra were recorded on a Varian Mercury400 MHz instrument and chemical shifts are expressed in parts permillion (ppm, δ) relative to TMS as the internal standard. Mass spectrawere obtained on a Thermo Finnigan LCQ-Deca (injection volume 5 uL,XTerra MS-C₁₈ 3.5 μm 2.1×50 mm column, XTerra MS-C₁₈ 5 μm 2.1×20 mmguard column), ESI source, analytical HPLC was performed on an HP1050(injection volume 5 μl, XTerra RP-C₁₈ 5 μm 4.6×250 mm column, with anXTerra MS-C₁₈ 5 μm 2.1×20 mm guard column), and preparative HPLC wasperformed on an Agilent 1100 Prep-LC with various columns and conditionsdepending on the compound. GCMS was performed on either an AgilentTechnology 6890N or Shimadzu QP5000/17A instrument.

All reactions were performed in flame-dried or oven-dried glasswareunder a positive pressure of dry nitrogen or dry argon and were stirredmagnetically unless otherwise indicated. Chemicals were purchased fromstandard commercial vendors and used as received unless otherwise noted.Otherwise their preparation is facile and known to one of ordinary skillin the art, or it is referenced or described herein. Yields are notoptimized. The chemical names were generated using the ISIS AutoNom andACD labs software.

Abbreviations and Acronyms

When the following abbreviations are used herein, they have thefollowing meaning: Ac₂O acetic anhydride anhy Anhydrous n-BuOH n-butanolt-BuOH t-butanol CD₃OD methanol-d₄ Celite ® diatomaceous earth filteragent,  ® Celite Corp. CH₂Cl₂ methylene chloride DCM dichloromethaneCI-MS chemical ionization mass spectroscopy conc concentrated decdecomposition bs broad singlet br broad DME dimethoxyethane DMFN,N-dimethylformamide DMSO dimethylsulfoxide DMSO-d₆dimethylsulfoxide-d₆ ELSD evaporative light scattering device EtOAcethyl acetate EtOH ethanol (100%) Et₂O diethyl ether Et₃N triethylamineHPLC ESI-MS high performance liquid chromatography-electrospray massspectroscopy MPLC medium pressure liquid chromatography NMR nuclearmagnetic resonance spectroscopy TOF-MS time-of-flight-mass spectroscopyNMM 4-methylmorpholine Ph₃P triphenylphosphine Pd(dppf)Cl₂ [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd(PPh₃)₄tetrakis(triphenylphosphine)palladium(0) Pd(OAc)₂ palladium(II) acetateP(O)Cl₃ phosphorous oxychloride R_(f) TLC retention factor RT retentiontime (HPLC) rt room temperature THF tetrahydrofuran TFA trifluoroaceticacid TLC thin layer chromatography LC-MS (ESI) liquidchromatography-mass spectroscopy (electrospray ionization) DIEAdiisopropylethylamine TFAA trifluoroacetic anhydride MsClmethanesulfonylchloride AcOH acetic acid HCl hydrochloric acid H₂SO₄sulfuric acid HNO₃ nitric acid HBr hydrobromic acid CDCl₃ chloroform-d₃CHCl₃ chloroform H₂O water NaOAc sodium acetate KOH potassium hydroxideNaOH sodium hydroxide NaCl sodium chloride NaHCO₃ sodium bicarbonateNa₂CO₃ sodium carbonate K₂CO₃ potassium carbonate Na₂SO₄ sodium sulfateMgSO₄ magnesium sulfate MeOH methanol SiO₂ silica gel K₃PO₄ potassiumphosphate NH₄Cl ammonium chloride AIBN 2,2′-axo bisisobutyronitrileBarton's base 2-t-butyl-1,1,3,3-tetramethylguanidine DMAP N,N-Dimethylaminopyridine LG leaving group MsCl methanesulfonyl chloride TsClp-toluenesulfonyl chloride PG protecting group Xantphos4,5-bis(diphenylphosphino)-9,9-dimethyl xanthane

General procedures

General Method of Preparation of Intermediates

The substituted alcohols which are either commercially available orprepared according to known literature procedure. These substitutedalcohols are converted to corresponding leaving group (Cl, Br, OMs orOTs) in accordance with synthetic methods well known to the skilledperson. General methods for the preparation of the compounds are givenbelow, and the preparation of representative compounds is specificallyillustrated in the experimental section.

FIG. 1

-   Reagents: i) SOCl₂, CHCl₃ or CBr₄, PPh₃/PPh₃-polymer, DCM or    CH₃SO₂Cl, NEt₃, DCM, or pTsCl, NEt₃, DMAP, DCM

FIG. 2

The 8-bromoadenine 2 was prepared by known method (US 2005/0049263). Thecompound 4 may be obtained either by nucleophilic attack of thearylthiolate anion on bromoadenine (US 2005/0049263) or bycopper-catalyzed coupling of aryliodides with mercaptoadenine 3 usingCuI/neocuproine as catalyst and t-BuONa/DMF as the base/solventcombination at 60-110° C. (J. Med. Chem., 2005, 48, 2892). Alternatively4 can be prepared by palladium catalysed coupling of aryl halides withmercaptoadenine 3. The derivatives of 8-arylsulfanyl adenine 4 werealkylated using various alkylating agents in the presence of base at30-110° C. in DMF for 1-18 h. Formation of the mixture of regioisomers 5and 6 were observed by HPLC and LC-MS analysis. At the end of thisperiod solvent was evaporated or after aqueous and organic work up, theorganic layer was collected and was dried over Na₂SO₄. After removalorganic solvent and preparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm(waters), Mobile phase: solvent A: Water HPLC grade containing 0.01%TFA, and solvent B: acetonitrile containing 0.01% TFA, general elutinggradient—solvent B 15% to 80% over 15 to 25 minutes run time]purification, N-3 and N-9 alkylated products are isolated as atrifluoroacetate salt.

General Method of Preparation of Intermediates

Intermediate 1

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine

To 250 mL flask was charged with 8-mercaptoadenine (2.00 g, 11.98 mmol),5,6-dibromo-benzo-[1,3]dioxole (6.70 g, 24.0 mmol), Pd₂dba₃ (0.548 g,0.599 mmol), Xantphos (0.693 g, 1.20 mmol), K₂CO₃ (3.31 g, 23.95 mmol),and dry dioxane (25 mL). The resulting mixture was heated at 100° C. for16 h under nitrogen. After cooling, the reaction mixture was filteredand washed with a 2/2/0.5 mixture of CH₂Cl₂, EtOAc, and MeOH. Thecombined filtrates were concentrated in vacuo. The dark brown residuewas purified by chromatography on SiO₂ (CH₂Cl₂/EtOAc/MeOH, 2/2/0/5) andsubsequent recrystallization from MeOH provided the title compound (1.4g, 32%). ¹H NMR (DMSO-d₆) δ 8.08 (s, 1H), 7.38 (s, 1H), 7.23 (s, 1H),6.12 (s, 2H).

Intermediates 2-36 were prepared according to the procedure describedfor intermediate 1. TABLE 1 Intermediate Structure Name and analyticalData 2

56-[(6-Amino-9 H-purin-8-yl)thio]- 1,3-benzodioxole-5-carbonitrile. ¹HNMR (DMSO-d₆) δ 8.08 (s, 1 H), 7.59 (s, 1 H), 7.29 (s, 1 H), 7.26-7.16(brs, 2 H), 6.23 (s, 2 H); TOF-MS [M + H]⁺ 315. 3

8-{[6-(Methoxymethyl)-1,3- benzodioxol-5-yl]thio}-9 H-purin-6- amine.TOF-MS [M + H]⁺ 332.08 4

8-[(7-Bromo-2,3-dihydro-1,4- benzodioxin-6-yl)thio]-9 H-purin-6- amine.LC-MS [M + H]⁺ 382.0 5

8-[(6-Bromo-2,2-difluoro-1,3- benzodioxil-5-yl)thio]-9 H-purin-6- amine.LC-MS [M + H]⁺ 403.9 6

8-[(2,2-Difluoro-1,3-benzodioxol-5- yl)thio]-9 H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.08 (s, 1 H), 7.70 (brs, 1 H), 7.47 (m, 1 H), 7.39 (m, 1H), 7.23 (brs, 2 H); LC-MS [M + H]⁺ 324.0 7

8-[(2-Bromo-4,5- dimethoxyphenyl)thio]-9 H-purin-6- amine. ¹H NMR(CD3OD) δ 8.09 (s, 1 H), 7.32 (s, 1 H), 7.30 (s, 1 H), 3.88 (s, 3 H),3.82 (s, 3 H); LC-MS [M + H]⁺ 382.0 8

2-[(6-Amino-9 H-purin-8-yl)thio]- 4,5-dimethoxybenzonitrile. TOF-MS [M +H]⁺ 329.08 9

8-[(2-Bromo-4,5- difluorophenyl)thio]-9 H-purin-6- amine. LC-MS [M + H]⁺292.0 10

8-{[4,5-Bis(benzyloxy)-2- bromophenyl]thio}-9 H-purin-6- amine. LC-MS[M + H]⁺ 533.5 11

8-[(4-Chloro-2,5- dimethoxyphenyl)thio]-9 H-purin-6- amine. LC-MS [M +H]⁺ 338.1 12

8-[(2-Chloro-3,5- dimethoxyphenyl)thio]-9 H-purin-6- amine. LC-MS [M +H]⁺ 338.1 13

8-[(3-Chloro-5-fluoro-4- methoxyphenyl)thio]-9 H-purin-6- amine. LC-MS[M + H]⁺ 326.2 14

6-[(6-Amino-9 H-purin-8- yl)thio]indan-1-one. LC-MS [M + H]⁺ 298.0 15

8-[(4-Methoxy-7-methyl-2,3- dihydro-1 H-inden-5-yl)thio]- 9 H-purin-6-amine. LC-MS [M + H]⁺ 328.3 16

8-[(5-Methoxy-1,3-benzoxazol-7- yl)thio]-9 H-purin-6-amine. LC-MS [M +H]⁺ 315.0 17

7-[(6-Amino-9 H-purin-8-yl)thio]-4- methyl-2 H-chromen-2-one. LC-MS [M +H]⁺ 326.0 18

6-[(6-Amino-9 H-purin-8-yl)thio]- 2 H-1,4-benzoxazin-3(4 H)-one. LC-MS[M + H]⁺ 315.9 19

6-[(6-Amino-9 H-purin-8-yl)thio]-7- bromo-2H-1,4-benzoxazin-3(4 H)- one.TOF-MS [M + H]⁺ 392.98 20

8-(2,3-Dihydro-1-benzofuran-5- ylthio)-9 H-purin-6-amine. LC-MS [M + H]⁺285.9 21

1-Acetyl-5-[(6-amino-9 H-purin-8- yl)thio]-6-chloro-1 H-indol-3-ylacetate. LC-MS [M + H]⁺ 416.0 22

3-[(6-Amino-9 H-purin-8-yl)thio]-4- methoxybenzonitrile. ¹H NMR(DMSO-d₆) δ 8.10 (s, 1 H), 7.83 (d, J = 8.8 Hz, 1 H), 7.62 (brs, 1 H),7.31 (brs, 2 H), 7.28 (d, J = 8.8 Hz, 2 H), 3.91 (s, 1 H); LC-MS [M +H]⁺ 299.1 23

8-[(5-Fluoro-2-methoxyphenyl)thio]- 9 H-purin-6-amine. ¹H NMR (DMSO-d₆)δ 8.11 (s, 1 H), 7.34 (brs, 2 H), 7.17-7.11 (m, 2 H), 6.89 (m, 1 H),3.82 (s, 3 H); LC-MS [M + H]⁺ 292.1 24

8-[(2-Methoxy-5- methylphenyl)thio]-9 H-purin-6- amine. ¹H NMR (DMSO-d₆)δ 8.08 (s, 1 H), 7.24 (brs, 2 H), 7.11 (d, J = 8.4 Hz, 1 H), 6.98 (d, J= 8.4 Hz, 1 H), 6.91 (s, 1 H), 3.77 (s, 3 H), 2,17 (s, 3 H); LC-MS [M +H]⁺ 288.2 25

8-{[2-(Cyclopentyloxy)-5- (trifluoromethoxy)phenyl]thio}-9 H-purin-6-amine. TOF-MS [M + H]⁺ 412.11 26

8-[(2-Chloro-5-nitrophenyl)thio]-9 H- purin-6-amine. LC-MS [M + H]⁺323.2 27

8-[(2-Methoxy-5-nitrophenyl)thio]- 9 H-purin-6-amine. LC-MS [M + H]⁺319.2 28

N-{4-[(6-Amino-9 H-purin-8- yl)thio]-3-chlorophenyl}acetamide. LC-MS[M + H]⁺ 335.0 29

8-[(3,5-Dimethoxyphenyl)thio]-9 H- purin-6-amine. LC-MS [M + H]⁺ 304.030

8-[(2-Chloro-5- methoxyphenyl)thio]-9 H-purin-6- amine. LC-MS [M + H]⁺308.0 31

8-[(3-Methyl-2-thienyl)thio]-9 H- purin-6-amine. LC-MS [M + H]⁺ 264.0 32

2-[(6-Amino-9 H-purin-8-yl)thio]- 4,6-dimethylnicotinonitrile. LC-MS[M + H]⁺ 298.0 33

methyl 2-[(6-amino-9 H-purin-8- yl)thio]isonicotinate. LC-MS [M + H]⁺303.0 34

8-[(4-Methoxypyridin-2-yl)thio]-9 H- purin-6-amine. LC-MS [M + H]⁺ 275.035

8-[(3-Bromopyridin-2-yl)thio]-9 H- purin-6-amine. LC-MS [M + H]⁺ 323.136

8-[(6-Methoxypyrimidin-4-yl)thio]- 9 H-purin-6-amine. LC-MS [M + H]⁺276.0

Intermediate 37

8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine

8-(2,5-Dimethoxy-phenylsulfonyl)-9H-purin-6-ylamine was preparedaccording to the know method (J. Med. Chem., 2006, 49, 817).

Intermediates 38-42 were prepared according to the known method (J. Org.Chem., 2004, 69, 3230

TABLE 2 Intermediate Structure Name and analytical Data 38

8-[(2,4- Dimethoxyphenyl)thio[-9 H- purin-6-amine. LC-MS [M + H]⁻ 304.139

8-[(4-Chlorophenyl)thio]-9 H- purin-6-amine. LC-MS [M + H]⁺ 278.13 40

4-[(6-Amino-9 H-purin-8- yl)thio]benzonitrile. LC-MS [M + H]⁺ 269.2 41

8-[(3,4,5- Trimethoxyphenyl)thio]-9 H- purine-6-amine. LC-MS [M + H]⁺334.1 42

8-(1,3-Benzodioxol-5-ylthio)- 9 H-purin-6-amine. LC-MS [M + H]+ 288.2

General Alkylation Procedure Examples 1 and 2

8-(2,5-Dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine and8-(2,5-dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

A mixture of 8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine (0.050g, 0.165 mmol), (2-Bromo-ethyl)-benzene (0.032 g, 0.165 mmol), andBarton's base (3.00 mmol) in DMF (1.3 mL) was heated at 90-100° C. for6-15 h. The reaction mixture was then allowed to reach ambienttemperature. After removal of solvent under reduced pressure, theresidue was purified by preparative HPLC and isolated via lyophilizationto give the N-9 isomer and the N-3 isomer.8-(2,5-Dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine: Yield9.0%, ¹H NMR (DMSO-d₆) δ 8.18 (s, 1H), 7.43 (bs, 2H), 7.26-7.16 (m, 3H),7.04-7.00 (m, 3H), 6.85 (dd, J=8.8, 4.0 Hz, 1H), 6.45 (d, J=2.8 Hz, 1H),4.37 (t, J=7.2 Hz, 2H), 3.74 (s, 3H), 3.60 (s, 3H), 2.97 (t, J=7.2 Hz,2H); LC-MS (MHz) 408.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine: Yield8.0%, ¹H NMR (DMSO-d₆) δ 7.71 (s, 1H), 7.29-7.12 (m, 5H), 6.90 (d, J=8.8Hz, 1H), 6.88 (d, J=6.4 Hz, 1H), 6.68 (dd, J=8.8, 2.8 Hz, 1H), 4.33 (t,J=7.2 Hz, 2H), 3.77 (s, 3H), 3.58 (s, 3H), 3.15 (t, J=7.2 Hz, 2H); LC-MS(MHz) δ08.1.

Examples 3-223 listed below were prepared analogously to the proceduredescribed for examples 1 and 2 and are isolated as a trifluoroacetatesalts after preparative HPLC purification Example 3

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(3-bromo-propyl)-benzene by a procedure similar to examples 1 and 2.

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine:Yield 21%, ¹H NMR (DMSO-d₆) δ 8.17 (s, 1H), 7.45 (bs, 2H), 7.25-7.00 (m,6H), 6.85 (dd, J=8.8, 2.6, 1H), 6.74 (d, J=2.8 Hz, 1H), 4.19 (t, J=7.6Hz, 2H), 3.75 (s, 3H), 3.59 (s, 3H), 2.60 (t, J=7.6 Hz, 2H), 1.94 (m,2H); LC-MS [M+H]⁺ 422.1.

Examples 4 and 5

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine and8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

The title compounds were prepared from8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine: Yield31%, ¹H NMR (DMSO-d₆) δ 8.32 (s, 1H), 7.28-7.19 (m, 3H), 7.08-7.05 (m,2H), 6.95 (m, 3H), 6.06 (s, 2H), 4.43 (t, J=6.8 Hz, 2H), 3.02 (t, J=6.8Hz, 2H); LC-MS [M+H]⁺ 392.1.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine. Yield13%, ¹H NMR (DMSO-d₆) δ 8.35 (s, 1H), 8.17 (bs, 2H), 7.34-7.10 (m, 8H),6.16 (s, 2H), 4.53 (t, J=6.8 Hz, 2H), 3.16 (t, J=6.8 Hz, 2H); LC-MS[M+H]⁺ 392.1.

Example 6

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine

The title compound was prepared from8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(3-bromo-propyl)-benzene by a procedure similar to example 1 and 2.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine:¹H NMR (DMSO-D₆) δ 8.37 (s, 1H), 7-29-7.11 (m, 5H), 7.05 (s, 1H), 6.96(s, 2H), 7.07 (s, 2H), 4.21 (t, J=7.4 Hz, 2H), 2.59 (t, J=7.4 Hz, 2H),1.97 (q, J=8.4 Hz, 2H); LC-MS [M+H]⁺ 406.13.

Example 7

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine

The title compound was prepared from8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-nitro-benzene by a procedure similar to examples 1and 2.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-[2(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 43%, ¹H NMR (DMSO-d₆) δ 8.14 (s, 1H), 8.09 (d, J=8.8 Hz, 2H), 7.38(bs, 2H), 7.31 (d, J=8.8 Hz, 2H), 6.88-6.82 (m, 3H), 6.02 (s, 2H), 4.47(t, J=6.8 Hz, 2H), 3.20 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 437.1.

Example 8

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-nitro-benzene by a procedure similar to examples 1and 2. The compound was purified by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 35%, ¹H NMR (DMSO-d₆) δ 8.18 (s, 1H), 8.0 (d, J=8.8 Hz, 2H), 7.46(bs, 2H), 7.26 (d, J=8.8 Hz, 2H), 6.96 (d, J=9.2, 1H), 6.77 (dd, J=8.8,3.2 Hz, 1H), 6.27 (d, J=3.2 Hz, 1H), 4.50 (t, J=6.8 Hz, 2H), 3.75 (s,3H), 3.56 (s, 3H), 3.22 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 453.5.

Examples 9 and 10

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-fluoro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 20%, ¹H NMR (DMSO-d₆) δ 8.30 (s, 1H), 7.05-7.01 (m, 5H), 6.88 (dd,J=8.8, 2.8 Hz, 1H), 6.56 (d, J=2.8 Hz, 1H), 4.43 (t, J=6.8 Hz, 2H), 3.73(s, 3H), 3.62 (s, 3H), 3.02 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 426.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 17%, LC-MS [M+H]⁺ 426.1.

Examples 11 and 12

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-fluoro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 33%, ¹H NMR (DMSO-d₆) δ 8.27 (s, 1H), 8.10 (bs, 2H), 7.07-7.04 (m,4H), 6.95-6.93 (m, 3H), 6.02 (s, 2H), 4.41 (t, J=6.8 Hz, 2H), 3.02 (t,J=6.8 Hz, 2H); LC-MS [M+H]⁺ 410.1.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 11%, ¹H NMR (DMSO-d₆) δ 8.35 (s, 1H), 8.23 (bs, 2H), 7.33-7.09 (m,7H), 6.15 (s, 2H), 4.51 (t, J=7.2 Hz, 2H), 3.15 (t, J=7.2 Hz, 2H); LC-MS[M+H]⁺ 410.1.

Examples 13 and 14

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine:Yield 38%, ¹H NMR (DMSO-d₆) δ 8.31 (s, 1H), 7.37 (s, 1H), 7.26-7.18 (m,3H), 7.09-7.06 (m, 2H), 6.75 (s, 1H), 6.09 (s, 2H), 4.42 (t, J=7.2 Hz,2H), 3.05 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 472.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine:Yield 25%, ¹H NMR (DMSO-d₆) δ 8.33 (s, 1H), 7.52 (s, 1H), 7.41 (s, 1H),7.30-7.12 (m, 5H), 6.18 (s, 2H), 4.52 (t, J=6.8 Hz, 2H), 3.17 (t, J=6.8Hz, 2H); LC-MS [M+H]⁺ 472.0.

Examples 15 and 16

8-(2,4-Dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine and8-(2,4-dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

The title compounds were prepared from8-(2,4-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(2,4-Dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine: Yield29%, ¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 7.82 (bs, 2H), 7.29-7.18 (m, 4H),7.09 (dd, J=8.4, 1.6 Hz, 2H), 6.65 (d, J=2.4 Hz, 1H), 6.55 (dd, J=8.8,2.8, 1H), 4.42 (t, J=7.2 Hz, 2H), 3.77 (s, 3H), 3.74 (s, 3H), 3.01 (t,J=7.2 Hz, 2H); LC-MS [M+H]⁺ 408.1.8-(2,4-Dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine: Yield15%, ¹H NMR (DMSO-d₆) δ 7.62 (bs, 1H), 7.31-7.23 (m, 4H), 7.16-7.12 (m,2H), 6.83 (bs, 1H), 6.73 (bs, 1H), 4.52 (t, J=7.2 Hz, 2H), 3.86 (s, 3H),3.81 (s, 3H), 3.16 (t, J=7.2 Hz, 2H), LC-MS [M+H]⁺ 408.1.

Examples 17 and 18

8-(4-Chloro-phenylsulfonyl)-9-phenethyl-9H-purin-6-ylamine and8-(4-chloro-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

The title compounds were prepared from8-(4-chloro-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(4-Chloro-phenylsulfonyl)-9-phenethyl-9H-purin-6-ylamine: Yield 45%,¹H NMR (DMSO-d₆) δ 8.22 (s, 1H), 7.64 (bs, 2H), 7.44-7.40 (m, 2H),7.32-7.17 (m, 5H), 7.03 (dd, J=8.0, 1.6 Hz, 2H), 4.38 (t, J=7.2 Hz, 2H),3.01 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 382.0.8-(4-Chloro-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine: Yield 28%,¹H NMR (DMSO-d₆) δ 8.17 (s, 1H), 8.10 (bs, 2H), 7.60 (d, J=8.4 Hz, 2H),7.49 (d, J=8.8 Hz, 2H), 7.28-7.22 (m, 3H), 7.12 (dd, J=8.4, 1.6 Hz, 2H),4.49 (t, J=6.8 Hz, 2H), 3.16 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 382.0.

Examples 19 and 20

4-(6-Amino-9-phenethyl-9H-purin-8-ylsulfanyl)-benzonitrile and4-(6-amino-3-phenethyl-3H-purin-8-ylsulfanyl)-benzonitrile

The title compounds were prepared from4-(6-amino-9H-ylsulfanyl)-benzonitrile and (2-bromo-ethyl)-benzene by aprocedure similar to examples 1 and 2. The isomers were separated bypreparative HPLC.4-(6-Amino-9-phenethyl-9H-purin-8-ylsulfanyl)-benzonitrile: Yield 22%,¹H NMR (DMSO-d₆) δ 8.32 (s, 1H), 7.77 (dd, J=6.8, 2.0 Hz, 2H), 7.33 (dd,J=6.4, 2.0 Hz, 2H), 7.24-7.16 (m 3H), 7.01 (dd, J=8.0, 2.0 Hz, 2H), 4.42(t, J=7.2 Hz, 2H), 3.04 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 373.0.4-(6-Amino-3-phenethyl-3H-purin-8-ylsulfanyl)-benzonitrile: Yield, 16%,¹H NMR (DMSO-d₆) δ 8.47 (bs, 1H), 8.31 (bs, 1H), 8.25 (s, 1H), 7.85 (dd,J=8.4, 1.6 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 7.30-7.20 (m, 3H), 7.13 (dd,J=8.4, 1.6 Hz, 2H), 4.52 (t, J=7.2 Hz, 2H), 3.18 (t, J=7.2 Hz, 2H);LC-MS [M+H]⁺ 373.0.

Examples 21 and 22

9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(3,4-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-bromo-ethyl)-1,2-dimethoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 52%, ¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.02 (d, J=8.8 Hz, 1H), 6.87(dd, J=9.2, 2.8 Hz, 1H), 6.77 (d, J=8.4 Hz, 1H), 6.58 (d, J=1.6 Hz, 1H),6.54 (d, J=3.2 Hz, 1H), 6.49 (dd, J=8.0, 2.4 Hz, 1H), 4.41 (t, J=7.2 Hz,2H), 3.73 (s, 3H), 3.68 (s, 3H), 3.64 (s, 3H), 3.61 (s, 3H), 2.94 (t,J=7.2 Hz, 2H); LC-MS [M+H]⁺ 468.2.3-[2-(3,4-Dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine.Yield 26%, ¹H NMR (DMSO-d₆) δ 8.25 (s, 1H), 8.15 (bs, 2H), 6.82 (d,J=8.4 Hz, 2H), 6.73 (bs, 2H), 6.58 (d, J=6.4 Hz, 2H), 4.52 (t, J=6.4 Hz,2H), 3.77 (s, 3H), 3.71 (s, 3H), 3.70 (s, 3H), 3.68 (s, 3H), 3.09 (t,J=6.4 Hz, 2H); LC-MS [M+H]⁺ 468.1

Examples 23 and 24

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-methyl-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine:Yield 37%, ¹H NMR (DMSO-d₆) δ 8.24 (s, 1H), 7.77 (bs, 2H), 7.03 (m, 3H),6.92 (d, J=8.0 Hz, 2H), 6.86 (dd, J=8.8, 3.2 Hz, 1H), 6.50 (d, J=2.8 Hz,1H), 4.36 (t, J=7.2 Hz, 2H), 3.74 (s, 3H), 3.60 (s, 3H), 2.94 (t, J=7.2Hz, 2H), 2.23 (s, 3H); LC-MS [M+H]⁺ 422.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine:Yield 28%, ¹H NMR (DMSO-d₆) δ 8.84 (s, 1H), 8.34 (s, 1H), 8.20 (bs, 2H),7.25-6.99 (m, 7H), 4.50 (t, J=7.2 Hz, 2H), 3.76 (s, 3H), 3.73 (s, 3H),3.12 (t, J=7.2 Hz, 2H) 2.25 (s, 3H); LC-MS [M+H]⁺ 422.1.

Examples 25 and 26

9-[2-(2-Chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-chloro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.9-[2-(2-Chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 18%, ¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 7.82 (bs, 2H), 7.36 (dd,J=8.0, 1.2 Hz, 1H), 7.24-7.15 (m, 2H), 7.03-6.99 (m, 2H), 6.85 (dd,J=9.2, 3.2 Hz, 1H), 6.47 (d, J=2.8 Hz, 1H), 4.46 (t, J=7.2 Hz, 2H), 3.73(s, 3H), 3.61 (s, 3H), 3.16 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 442.1.3-[2-(2-Chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield, 11%, ¹H NMR (DMSO-d₆) δ 8.34 (s, 1H), 8.16 (bs, 1H), 7.41 (m,1H), 7.29-7.11 (m, 6H), 4.56 (t, J=6.8 Hz, 2H), 3.76 (s, 3H), 3.72 (s,3H), 3.30 (t, J=6.8 Hz, 2H), LC-MS [M+H]⁺ 442.1.

Examples 27 and 28

9-[2-(2,4-Dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2,4-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenyl-sulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2,4-dichloro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(2,4-Dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 41%, ¹H NMR (DMSO-d₆) δ 8.28 (s, 1H), 7.50 (d, J=2.8 Hz, 1H), 7.25(dd, J=8.4, 2.0 Hz, 1H), 7.05 (d, J=8.4 Hz, 1H), 7.01 (d, J=9.2 Hz, 1H),6.86 (dd, J=9.2, 2.8 Hz, 1H), 6.52 (d, J=2.8 Hz, 1H), 4.48 (t, J=6.8 Hz,2H), 3.73 (s, 3H), 3.62 (s, 3H), 3.17 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺476.1.3-[2-(2,4-Dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenyl-sulfanyl)-3H-purin-6-ylamine:Yield 13%, ¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 8.15 (bs, 2H), 7.58 (d,J=2.0 Hz, 1H), 7.36 (dd, J=8.4, 2.0 Hz, 1H), 7.26 (d, J=8.0 Hz, 1H),7.22-7.09 (m, 3H), 4.54 (t, J=6.8 Hz, 2H), 3.76 (s, 3H), 3.73 (s, 3H),3.29 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 476.1.

Examples 29 and 30

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-fluoro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 37%, ¹H NMR (DMSO-d₆) δ 8.27 (s, 1H), 7.28-7.22 (m, 1H), 7.12-7.00(m, 4H), 6.87 (dd, J=8.8, 3.2 Hz, 1H), 6.55 (d, J=3.2 Hz, 1H), 4.45 (t,J=6.8, Hz, 2H), 3.72 (s, 3H), 3.62 (s, 3H), 3.08 (t, J=6.8, 2H); LC-MS[M+H]⁺ 426.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield, 18%, ¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 8.19 (bs, 2H), 7.33-7.08(m, 7H), 4.55 (t, J=7.2 Hz, 2H), 3.76 (s, 3H), 3.73 (s, 3H), 3.23 (t,J=7.2 Hz, 2H); LC-MS [M+H]⁺ 426.1.

Examples 31 and 32

9-[2-(4-Chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(4-chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-chloro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.9-[2-(4-Chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 7%, ¹H NMR (DMSO-d₆) δ 8.21 (s, 1H), 7.29 (br d, J=8.8 Hz, 2H),7.05 (br d, J=8.8 Hz, 2H), 6.71 (s, 2H), 4.41 (t, J=7.6 Hz, 2H), 3.71(s, 6H), 3.63 (s, 3H), 2.99 (t, J=7.6 Hz, 2H); LC-MS [M+H]⁺ 472.0.3-[2-(4-Chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 7%, ¹H NMR (DMSO-d₆) δ 8.19 (s, 1H), 7.29-7.26 (m, 2H), 7.13-7.10(m, 4H), 4.60 (t, J=6.8 Hz, 2H), 3.88 (s, 6H), 3.86 (s, 3H) 3.23 (t,J=6.8 Hz, 2H); LC-MS [M+H]⁺ 472.1.

Examples 33 and 34

8-(-6-Iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamineand8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

The title compounds were prepared from8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(-6-Iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine:Yield 11%, ¹H NMR (DMSO-d₆) δ 8.31 (s, 1H), 7.49 (s, 1H), 7.27-7.19 (m,3H), 7.10-7.09 (m, 2H), 6.74 (s, 1H), 6.07 (s, 2H), 4.41 (t, J=7.2 Hz,2H), 3.04 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 518.0.8-(6-Iodo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine:Yield 6%, ¹H NMR (CD₃OD) δ 8.06 (s, 1H), 7.56 (s, 1H), 7.38 (s, 1H),7.29-7.18 (m, 3H), 7.11-7.08 (m, 2H), 6.13 (s, 2H), 4.59 (t, J=7.2 Hz,2H), 3.22 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 518.0.

Examples 35 and 36

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-methoxy-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-methoxy-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 27%, ¹H NMR (DMSO-d₆) δ 8.24 (s, 1H), 7.13 (t, J=8.0 Hz, 1H), 7.01(d, J=6.8 Hz, 1H), 6.86 (dd, J=8.8, 3.2 Hz, 1H), 6.75 (m, 1H), 6.60-6.51(m, 2H), 6.50 (d, J=3.2 Hz, 1H), 4.40 (t, J=7.2 Hz, 2H), 3.74 (s, 3H),3.67 (s, 3H), 3.60 (s, 3H), 2.96 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 438.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(3-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 15%, ¹H NMR (DMSO-d₆) δ 8.32 (bs, 1H), 7.24-7.09 (m, 4H), 6.79 (d,J=8.0 Hz, 1H), 6.72 (bs, 1H), 6.67 (d, J=7.6 Hz, 1H), 4.53 (t, J=7.2 Hz,2H), 3.77 (s, 3H), 3.71 (s, 3H), 3.70 (s, 3H), 3.15 (t, J=7.2 Hz, 2H);LC-MS [M+H]⁺ 438.1.

Examples 37 and 38

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-fluoro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 19%, ¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 7.82 (bs, 2H), 7.24 (dd,J=6.0, 2.0 Hz 1H), 7.03-6.97 (m, 2H), 6.90-6.85 (m, 2H), 6.82 (d, J=7.2Hz, 1H), 6.51 (d, J=2.8 Hz, 1H), 4.43 (t, J=7.2 Hz, 2H), 3.74 (s, 3H),3.61 (s, 3H), 3.03 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 426.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 9%, ¹H NMR (DMSO-d₆) δ 8.35 (s, 1H), 8.11 (bs, 2H), 7.31 (q, J=8.0Hz, 1H), 7.23-7.01 (m, 5H), 6.94 (d, J=7.2 Hz, 1H), 4.55 (t, J=7.2 Hz,2H), 3.77 (s, 3H), 3.72 (s, 3H), 3.20 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺426.1.

Examples 39 and 40

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-chloro-2-fluorophenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-chloro-2-fluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-chloro-2-fluorophenyl)-ethyl]-9H-purin-6-ylamine:Yield 20%, ¹H NMR (DMSO-d₆) δ 8.24 (s, 1H), 7.36 (s, 1H), 7.31-7.27 (m,1H), 7.16-7.04 (m, 2H), 6.72 (s, 1H), 6.10 (s, 2H), 4.44 (t, J=7.1 Hz,2H), 3.12 (t, J=7.1, Hz, 2H); LC-MS [M+H]⁺ 523.9.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 9%, ¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 7.49 (s, 1H), 7.39-7.30 (m,2H), 7.22-7.19 (m, 2H), 6.18 (s, 2H), 4.58 (t, J=7.6 Hz, 2H), 3.22 (t,J=7.6 Hz, 2H); LC-MS [M+H]⁺ 523.9.

Examples 41 and 42

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pentafluorophenyl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2,3,4,5,6-pentafluoro-benzene by a procedure similarto examples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine:Yield 41%, ¹H NMR (DMSO-d₆) δ 8.19 (s, 1H), 7.38 (s, 1H), 6.79 (s, 1H)6.13 (s, 2H), 4.44 (t, J=7.4 Hz, 2H), 3.22 (t, J=7.4 Hz, 2H); LC-MS[M+H]⁺ 561.9.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pentafluorophenyl-ethyl)-3H-purin-6-ylamine:Yield 13%, LC-MS [M+H]⁺ 561.9.

Examples 43 and 44

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-phenyl-propyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(3-bromo-propyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine:Yield 20%, ¹H NMR (DMSO-d₆) δ 8.32 (s, 1H), 7.40 (s, 1H), 7.28-7.23 (m,2H), 7.19-7.13 (m, 3H), 6.92 (s, 1H), 6.92 (s, 1H) 6.10 (s, 2H). 4.23(t, J=7.2 Hz, 2H), 2.59 (t, J=7.2 Hz, 2H), 2.03-1.95 (m, 2H); LC-MS[M+H]⁺ 486.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-phenyl-propyl)-3H-purin-6-ylamine:Yield 4%, ¹H NMR (DMSO-d₆) δ 8.59 (s, 1H), 8.20 (s, 1H), 7.49 (s, 1H),7.38 (s, 1H), 7.27-7.23 (m, 2H), 7.18-7.15 (m, 3H), 6.17 (s, 2H). 4.33(t, J=6.8 Hz, 2H), 2.63 (t, J=7.6 Hz, 2H), 2.23-2.15 (m, 2H); LC-MS[M+H]⁺ 486.0.

Examples 45 and 46

9-Phenethyl-8-(3,4,5-trimethoxy-phensulfanyl)-9H-purin-6-ylamine and3-phenethyl-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.9-Phenethyl-8-(3,4,5-trimethoxy-phensulfanyl)-9H-purin-6-ylamine: Yield38%, ¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.27-7.18 (m, 3H), 7.06-7.04 (m,2H), 6.74 (s, 2H), 4.17 (t, J=6.8 Hz, 2H), 3.71 (s, 6H), 3.64 (s, 3H),2.97 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 438.1.3-Phenethyl-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 14%, ¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 7.31-7.21 (m, 3H), 7.15-7.13(m, 2H), 7.10 (s, 2H), 4.54 (t, J=6.8 Hz, 2H), 3.80 (s, 6H), 3.73 (s,3H) 3.17 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 438.1.

Examples 47 and 48

9-(3-Phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-(3-phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(3-bromo-propyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.9-(3-Phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 34%, ¹H NMR (DMSO-d₆) δ 8.30 (s, 1H), 7.26-7.22 (m, 2H), 7.16 (tt,J=7.6, 1.2 Hz, 1H), 7.12-7.10 (m, 2H), 6.78 (s, 2H), 4.24 (t, J=7.2 Hz,2H), 3.72 (s, 6H), 3.63 (s, 3H), 2.56 (t, J=7.6 Hz, 2H), 1.94 (tt,J=7.6, 7.2 Hz, 2H); LC-MS [M+H]⁺ 452.0.3-(3-Phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield, 13%, ¹H NMR (DMSO-d₆) δ 8.61 (s, 1H), 7.27-7.23 (m, 2H),7.18-7.15 (m, 3H), 7.06 (s, 2H), 4.35 (t, J=7.2 Hz, 2H), 3.77 (s, 6H),3.71 (s, 3H) 2.64 (t, J=7.2 Hz, 2H), 2.20 (quintet, J=7.2 Hz, 2H); LC-MS[M+H]⁺ 452.0.

Examples 49 and 50

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamineand8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-1H-pyrrole by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine:Yield 27%, ¹H NMR (CD₃OD) δ 8.24 (s, 1H), 7.09 (dd, J=8.0, 1.6 Hz, 1H),7.00 (d, J=1.6 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H), 6.42 (t, J=2.0 Hz, 2H),6.03 (s, 2H), 5.98 (t, J=2.0 Hz, 2H), 4.58-4.55 (m, 2H), 4.41-4.38 (m,2H); LC-MS [M+H]⁺ 381.2.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine:Yield 16%, ¹H NMR (CD₃OD) δ 7.60 (s, 1H), 7.32 (dd, J=8.0, 1.6 Hz, 1H),7.25 (d, J=1.6 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.49 (t, J=2.4 Hz, 2H),6.13 (s, 2H), 6.02 (t, J=2.0 Hz, 2H), 4.67 (br t, J=6.0 Hz, 2H), 4.40(br t, J=6.0 Hz, 2H); LC-MS [M+H]⁺ 381.1.

Examples 51 and 52

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-pyrrol-1-yl-propyl)-9H-purin-6-ylamineand8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-pyrrol-1-yl-propyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(3-bromo-propyl)-1H-pyrrole by a procedure similar to examples 1 and2. The isomers were separated by preparative HPLC.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-pyrrol-1-yl-propyl)-9H-purin-6-ylamine:Yield 23%, ¹H NMR (CD₃OD) δ 8.18 (s, 1H), 7.06 (dd, J=8.0, 1.6 Hz, 1H),7.00 (d, J=1.6 Hz, 1H), 6.88 (d, J=8.0 Hz, 1H), 6.69 (t, J=2.4 Hz, 2H),6.04 (t, J=2.4 Hz, 2H), 6.02 (s, 2H), 4.20 (br t, J=7.6 Hz, 2H), 4.01(t, J=6.8 Hz, 2H), 2.21 (quintet, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 395.1.8-(Benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-pyrrol-1-yl-propyl)-3H-purin-6-ylamine:Yield 11%, ¹H NMR (CD₃OD) δ 8.31 (s, 1H), 7.29 (dd, J=8.0, 2.0 Hz, 1H),7.21 (d, J=2.0 Hz, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.60 (t, J=2.4 Hz, 2H),6.11 (s, 2H), 5.96 (t, J=2.4 Hz, 2H), 4.35 (t, J=6.8 Hz, 2H), 4.03 (t,J=6.8 Hz, 2H), 2.45 (quintet, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 395.1.

Examples 53 and 54

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-chloro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-chloro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 32%, ¹H NMR (CD₃OD) δ 8.18 (s, 1H), 7.34 (br d, J=7.2 Hz, 1H),7.22 (br t, J=7.2 Hz, 1H), 7.20 (s, 1H), 7.14 (br t, J=7.2 Hz, 1H), 7.02(br d, J=7.2 Hz, 1H), 6.89 (s, 1H), 6.05 (s, 2H), 4.57 (t, J=6.4 Hz,2H), 3.35 (t, J=6.4 Hz, 2H); LC-MS [M+H]⁺ 506.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-chloro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 16%, ¹H NMR (CD₃OD) δ 8.12 (s, 1H), 7.37-7.34 (m, 3H), 7.26-7.18(m, 2H), 7.14 (m, 1H), 6.16 (s, 2H), 4.64 (t, J=6.8 Hz, 2H), 3.38 (t,J=6.8 Hz, 2H); LC-MS [M+H]⁺ 506.0.

Examples 55 and 56

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and2-(2-bromo-ethyl)-1,3,5-trimethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 18%, ¹H NMR (DMSO-d₆) δ 8.39 (s, 1H), 7.04 (d, J=9.0 Hz, 1H),6.90-6.81 (m, 3H), 6.51 (s, 1H), 4.21 (t, J=8.8 Hz, 2H), 3.77 (s, 3H),3.61 (s, 3H), 3.00-2.91 (m, 2H), 2.27 (s, 6H), 2.19 (s, 3H); LC-MS[M+H]⁺ 450.20.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 6%, ¹H NMR (DMSO-d₆) δ 8.52 (s, 1H), 7.28-7.09 (m, 3H), 6.82 (s,2H), 4.30 (t, J=13.3 Hz, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 3.10 (t,J=15.1 Hz, 2H), 2.19 (s, 9H); LC-MS [M+H]⁺ 450.20.

Examples 57 and 58

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-phenyl-butyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(1-bromomethyl-propyl)-benzene by a procedure similar to examples 1 and2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine:Yield 25%, ¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.36 (s, 1H), 7.27-7.09 (m,5H), 6.69 (s, 1H), 6.10 (s, 2H), 4.49-4.30 (m, 2H), 3.21-3.11 (m, 1H),1.72-1.63 (m, 2H), 0.70 (t, J=7.6 Hz, 3H); LC-MS [M+H]⁺ 499.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-phenyl-butyl)-3H-purin-6-ylamine:Yield 8%, ¹H NMR (DMSO-d₆) δ 8.17 (s, 1H), 7.51 (s, 1H), 7.38 (s, 1H),7.28-7.09 (m, 5H), 6.19 (s, 2H), 4.61-4.52 (m, 1H), 4.47-4.42 (m, 1H),3.31-3.22 (m, 1H), 1.72-1.61 (m, 2H), 0.72 (t, J=7.1 Hz, 3H); LC-MS[M+H]⁺ 499.1.

Examples 59 and 60

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(1-bromomethyl-cyclopropyl)-4-methoxy-benzene by a procedure similarto examples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine:Yield 30%, ¹H NMR (CD₃OD) δ 7.45 (s, 1H), 7.26 (s, 1H), 7.19 (s, 1H),7.02 (d, J=8.8 Hz, 2H), 6.78 (d, J=8.9 Hz, 2H), 6.10 (s, 2H) 4.49 (s,2H), 3.72 (s, 3H), 1.20-1.18 (m, 2H), 0.91-0.88 (m, 2H); LC-MS [M+H]⁺527.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-3H-purin-6-ylamine:Yield 9%, ¹H NMR (CD₃OD) δ 8.16 (br s, 1H), 7.16 (s, 1H), 7.02 (d, J=8.8Hz, 2H), 6.81 (s, 1H), 6.76 (d, J=8.8 Hz, 2H), 6.04 (s, 2H), 4.40 (s,2H), 3.72 (s, 3H), 1.31-1.26 (m, 2H), 0.89-0.82 (m, 2H); LC-MS [M+H]⁺527.0.

Examples 61 and 62

9-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand)3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(1-bromomethyl-cyclobutyl)-4-chloro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 10%, ¹H NMR (DMSO-d₆) δ 8.28 (s, 1H), 7.32-7.28 (m, 2H), 6.97-6.91(m, 3H), 6.85-6.81 (m, 1H), 6.52 (d, J=3.0 Hz, 1H), 4.59 (s, 2H) 3.62(s, 3H), 3.61 (s, 3H), 2.68-2.60 (m, 2H), 2.31-2.21 (m, 2H), 2.17-2.08(m, 1H), 1.83-1.75 (m, 1H); LC-MS [M+H]⁺ 482.10.3-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 4%, ¹H NMR (DMSO-d₆) δ 8.19 (s, 1H), 7.35-7.29 (m, 2H), 7.22-7.05(m, 3H), 6.98-6.95 (m, 2H), 4.66 (s, 2H) 3.78 (s, 3H), 3.76 (s, 3H),2.52-2.41 (m, 2H), 2.32-2.21 (m, 2H), 2.07-1.99 (m, 1H), 1.81-1.70 (m,1H); LC-MS [M+H]⁺ 482.10.

Examples 63 and 64

8-(4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanoneand1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-[4-(2-chloro-ethyl)-phenyl]-ethanone by a procedure similar toexamples 1 and 2. The isomers were separated by preparativeHPLC.1-(4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone:Yield 26%, ¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.17(d, J=8.0, 2H), 7.01 (d, J=8.8 Hz, 1H), 6.86 (dd, J=9.2, 2.8 Hz, 1H),6.49 (d, J=3.2 Hz, 1H), 4.50 (t, J=7.2 Hz, 2H), 3.74 (s, 3H), 3.60 (s,3H), 3.12 (t, J=7.2 Hz, 2H), 2.52 (s, 3H); TOF LC-MS [M+H]⁺ 450.16.1-(4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone:Yield 11%, ¹H NMR (DMSO-d₆) δ 8.37 (bs, 1H), 8.14 (bs, 2H), 7.88 (d,J=8.4 Hz, 2H), 7.30 (d, J=8.4 Hz, 2H), 7.26-7.06 (m, 3H), 4.57 (t, J=6.8Hz, 2H), 3.77 (s, 3H), 3.72 (s, 3H), 3.27 (t, J=7.2 Hz, 2H), 2.56 (s,3H); TOF LC-MS [M+H]⁺ 450.16.

Examples 65 and 66

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-1H-pyrrole by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine:Yield 26%, ¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.01 (d, J=9.2 Hz, 1H), 6.88(dd, J=9.2, 3.2 Hz, 1H), 6.55 (d, J=2.8 Hz, 1H), 6.43 (t, J=2.0 Hz, 2H),5.90 (t, J=2.0 Hz, 2H), 4.52 (t, J=6.4 Hz, 2H), 4.29 (t, J=6.4 Hz, 2H),3.71 (s, 3H), 3.62 (s, 3H); TOF LC-MS [M+H]⁺ 397.14.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine:Yield 16%, ¹H NMR (DMSO-d₆)

8.16 (bs, 1H), 7.81 (bs, 1H), 7.24-7.02 (m, 3H), 6.56 (m, 2H), 5.95 (m,2H), 4.62 (m, 2H), 4.46-4.34 (m, 2H), 3.77 (s, 3H), 3.73 (s, 3H); TOFLC-MS [M+H]⁺ 397.14.

Examples 67 and 68

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-naphthalene by a procedure similar to examples 1 and2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine:Yield 28%, ¹H NMR (DMSO-d₆) δ 8.33 (s, 1H), 8.13-8.10 (m, 1H), 7.94-7.92(m, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.56-7.52 (m, 2H), 7.37 (t, J=7.2 Hz,1H), 7.14 (d, J=6.0 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 6.86 (dd, J=9.2,2.8 Hz, 1H), 6.50 (d, J=3.2 Hz, 1H), 4.50 (t, J=6.4 Hz, 2H), 3.72 (s,3H), 3.60 (s, 3H), 3.45 (t, J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺ 458.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine:Yield 14%, ¹H NMR (DMSO-d₆) δ 8.19 (d, J=8.4 Hz, 1H), 8.11 (bs, 1H),7.95 (d, J=8.0 Hz, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.58-7.40 (m, 3H),7.32-7.26 (m, 2H), 7.17 (bs, 1H), 7.09 (bs, 1H), 4.60 (t, J=7.2 Hz, 2H),3.78 (s, 3H), 3.72 (s, 3H), 3.64 (t, J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺458.1.

Examples 69 and 70

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-methyl-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine:Yield 23%, ¹H NMR (DMSO-d₆) δ 8.31 (bs, 1H), 7.18-7.00 (m, 4H),6.90-6.84 (m, 2H), 6.56 (bs, 1H), 4.36 (t, J=7.2 Hz, 2H), 3.74 (s, 3H),3.61 (s, 3H), 2.98 (t, J=7.2 Hz, 2H), 2.26 (s, 3H); TOF LC-MS [M+H]⁺422.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine:Yield 15%, ¹H NMR (DMSO-d₆) δ 8.15 (bs, 1H), 7.24 (bs, 1H), 7.20-7.06(m, 5H), 6.99 (d, J=7.6 Hz, 1H), 4.46 (t, J=7.2 Hz, 2H), 3.76 (s, 3H),3.72 (s, 3H), 3.16 (t, J=7.2 Hz, 2H), 2.32 (s, 3H); TOF LC-MS [M+H]⁺422.1.

Examples 71 and 72

9-[2-(4-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(4-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-bromo-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.9-[2-(4-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 27%, ¹H NMR (DMSO-d₆) δ 8.24 (bs, 1H), 7.40 (dd, J=6.8, 2.0 Hz,2H), 7.02 (d, J=8.8 Hz, 1H), 6.98 (dd, J=6.4, 2.0 Hz, 2H), 6.87 (dd,J=8.8, 2.8 Hz, 1H), 6.50 (d, J=2.8 Hz, 1H), 4.41 (t, J=7.2 Hz, 2H), 3.74(s, 3H), 3.61 (s, 3H), 2.98 (t, J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺ 488.05.3-[2-(4-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 13%, ¹H NMR (DMSO-d₆) δ 8.15 (bs, 1H), 7.51-7.44 (m, 2H), 7.24(bs, 1H), 7.18 (d, J=8.4 Hz, 1H), 7.14-7.09 (m, 3H), 4.53 (t, J=6.8 Hz,2H), 3.76 (s, 3H), 3.73 (s, 3H), 3.16 (t, J=6.8 Hz, 2H); TOF LC-MS[M+H]⁺ 488.05.

Examples 73 and 74

9-[2-(2,3-Dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2,3-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2,3-dichloro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(2,3-Dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 14%, ¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 7.46 (dd, J=8.0, 1.6 Hz,1H), 7.16 (t, J=8.0 Hz, 1H), 7.0 (d, J=9.4 Hz, 1H), 6.95 (dd, J=7.6, 1.6Hz, 1H), 6.85 (dd, J=8.8, 3.2 Hz, 1H), 6.45 (d, J=2.8 Hz, 1H), 4.48 (t,J=7.2 Hz, 2H), 3.74 (s, 3H), 3.60 (s, 3H), 3.22 (t, J=7.2 Hz, 2H); TOFLC-MS [M+H]⁺ 476.0.3-[2-(2,3-Dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 10%, ¹H NMR (DMSO-d₆) δ 8.09 (bs, 2H), 7.50 (d, J=7.2 Hz, 1H),7.31-7.24 (m, 1H), 7.22-7.10 (m, 3H), 4.60-4.52 (m, 2H), 3.76 (s, 3H),3.71 (s, 3H), 3.40-3.30 (m, 2H); TOF LC-MS [M+H]⁺ 476.0.

Example 75 and 76

4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenoland4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-bromo-ethyl)-phenol by a procedure similar to examples 1 and 2.4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol:Yield 15%, ¹H NMR (DMSO-d₆) δ 9.24 (s, 1H), 8.19 (s, 1H), 7.53 (bs, 2H),7.02 (d, J=9.2 Hz, 1H), 6.85 (dd, J=8.0, 2.8 Hz, 2H), 6.81 (d, J=8.4 Hz,2H), 6.62 (d, J=8.4 Hz, 1H), 6.46 (d, J=2.8 Hz, 1H), 4.30 (t, J=7.6 Hz,2H), 3.74 (s, 3H), 3.60 (s, 3H), 2.85 (t, J=7.6 Hz, 2H); LC-MS [M+H]⁺424.1.4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol:Yield 7%, ¹H NMR (DMSO-d₆) δ 9.31 (bs, 1H), 8.28 (bs, 1H), 7.3-7.0 (m,3H), 6.90 (d, J=8.8 Hz, 2H), 6.66-6.59 (m, 2H), 4.46 (t, J=7.2 Hz, 2H),3.76 (s, 3H), 3.72 (s, 3H), 3.04 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 424.1.

Examples 77 and 78

9-[2-(3-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(3-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-bromo-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.9-[2-(3-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 24%, ¹H NMR (DMSO-d₆) δ 8.24 (s, 1H), 7.89 (bs, 2H), 7.37 (dd,J=8.0, 0.8 Hz, 1H), 7.24 (bs, 1H), 7.17 (t, J=8.0 Hz, 1H), 7.04-6.98 (m,2H), 6.88 (dd, J=8.8, 3.2 Hz, 1H), 6.53 (d, J=3.2 Hz, 1H), 4.41 (t,J=7.2 Hz, 2H), 3.75 (s, 3H), 3.62 (s, 3H), 3.00 (t, J=7.2 Hz, 2H); LC-MS[M+H]⁺ 486.1.3-[2-(3-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 13%, ¹H NMR (DMSO-d₆) δ 8.39 (bs, 1H), 8.15 (bs, 2H), 7.45-7.43(m, 2H), 7.29-7.12 (m, 2H), 7.19-7.09 (m, 3H), 4.54 (t, J=7.2 Hz, 2H),3.77 (s, 3H), 3.72 (s, 3H), 3.18 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 486.1.

Examples 79 and 80

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-chloro-ethyl)-3-trifluoromethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 10%, ¹H NMR (DMSO-d₆) δ 8.16 (s, 1H), 7.59 (bs, 2H), 7.52 (d,J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 7.34 (s, 1H), 7.28 (d, J=8.0 Hz,1H), 7.01 (d, J=9.2 Hz, 1H), 6.85 (d, J=6.0 Hz, 1H), 6.46 (bs, 1H), 4.44(t, J=6.8 Hz, 2H), 3.74 (s, 3H), 3.60 (s, 3H), 3.12 (t, J=6.8 Hz, 2H);LC-MS [M+H]⁺ 476.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 5%, ¹H NMR (DMSO-d₆) δ 8.38 (bs, 1H), 8.12 (bs, 1H), 7.64-7.42 (m,3H), 7.26-7.02 (m, 3H), 4.58 (m, 2H), 3.76 (s, 3H), 3.71 (s, 3H), 3.29(m, 2H); LC-MS [M+H]⁺ 476.1.

Examples 81 and 82

4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzoicacid and4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzoicacid

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-chloro-ethyl)-benzoic acid by a procedure similar to examples 1 and2. The isomers were separated by preparative HPLC. ¹H NMR (Acetone-d₆) δ8.27 (s, 1H), 7.91 (d, J=8.0 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 7.00 (d,J=8.8 Hz, 1H), 6.86 (dd, J=8.8, 3.2 Hz, 1H), 6.69 (d, J=3.2 Hz, 1H),4.55 (t, J=7.6 Hz, 2H), 3.81 (s, 3H), 3.67 (s, 3H), 3.21 (t, J=7.6 Hz,2H); TOF LC-MS [M+H]⁺ 452.14.

4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzoicacid: Yield 11%, ¹H NMR (CD₃OD) δ 8.19 (s, 1H), 7.93 (d, J=7.2 Hz, 2H),7.29 (s, 1H), 7.24 (d, J=7.6 Hz, 2H), 7.19 (s, 2H), 4.64 (t, J=8.0 Hz,2H), 3.81 (s, 6H), 3.36-3.28 (m, 2H); LC-MS [M+H]⁺ 452.1.

Example 83

8-(2,5-Dimethoxy-phenylsulfanyl)-3-(4-fluoro-benzyl)-3H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-bromomethyl-4-fluoro-benzene by a procedure similar to examples 1 and2. The compound was purified by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(4-fluoro-benzyl)-3H-purin-6-ylamine:Yield 34%, ¹H NMR (DMSO-d₆) δ 8.55 (s, 1H), 8.1 (bs, 2H), 7.51 (m, 2H),7.15 (m, 2H), 6.97 (m, 2H), 6.76 (dd, J=8.8, 2.8 Hz, 1H), 5.44 (s, 2H),3.74 (s, 3H), 3.50 (s, 3H); LC-MS [M+H]⁺ 412.1.

Example 84

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(4-nitro-benzyl)-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-bromomethyl-4-nitro-benzene by a procedure similar to examples 1 and2. The compound was purified by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(4-nitro-benzyl)-9H-purin-6-ylamine:Yield 10%, ¹H NMR (DMSO-d₆) δ 8.20 (s, 1H), 8.04 (d, J=6.8 Hz, 2H), 7.57(bs, 2H), 7.30 (d, 6.8 Hz, 2H), 6.88 (d, J=8.4 Hz, 1H), 6.70 (dd, J=9.2,3.2 Hz, 1H), 6.25 (d, J=2.8 Hz, 1H), 5.52 (s, 2H), 3.71 (s, 3H), 3.52(s, 3H); LC-MS [M+H]⁺ 439.1.

Examples 85 and 86

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-methoxy-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-methoxy-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 27%, ¹H NMR (DMSO-d₆) δ 8.26 (s, 1H), 7.19-7.15 (m, 1H), 7.00 (d,J=8.8 Hz, 1H), 6.89-6.73 (m, 4H), 6.47 (d, J=2.4 Hz, 1H), 4.42 (t, J=7.2Hz, 2H), 3.73 (s, 3H), 3.67 (s, 3H), 3.61 (s, 3H), 3.01 (t, J=7.2 Hz,2H); LC-MS [M+H]⁺ 438.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(2-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 11%, ¹H NMR (DMSO-d₆) δ 8.20 (bs, 1H), 7.26-7.16 (m, 3H),7.15-7.08 (m, 1H), 6.98 (dd, J=7.2, 1.6 Hz, 1H), 6.91 (d, J=7.2 Hz, 1H),6.83 (t, J=7.2 Hz, 1H), 4.51 (t, J=6.8 Hz, 2H), 3.76 (s, 3H), 3.70 (s,3H), 3.58 (s, 3H), 3.13 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 438.1.

Examples 87 and 88

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-phenyl)-butyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(1-bromomethyl-propyl)-benzene by a procedure similar to examples 1 and2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.28 (s, 1H), 7.26-7.18 (m, 3H), 7.08-7.01 (m, 3H),6.88 (dd, J=3.2, 9.0 Hz, 1H), 6.50 (d, J=2.9 Hz, 1H), 4.45-4.29 (m, 2H),3.74 (s, 3H), 3.60 (s, 3H), 3.15-3.05 (m, 1H), 1.71-1.59 (m, 2H), 0.65(t, J=7.3 Hz, 3H); LC-MS [M+H]⁺) 436.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-phenyl)-butyl)-3H-purin-6-ylamine:Yield 31%, ¹H NMR (DMSO-d₆) δ 8.20 (s, 1H), 7.31-7.08 (m, 8H), 4.63-4.51(m, 1H), 4.48-4.39 (m, 1H), 3.79 (s, 3H), 3.77 (s, 3H), 3.29-3.20 (m,1H), 1.75-1.61 (m, 2H), 0.73 (t, J=7.0 Hz, 3H); LC-MS [M+H]⁺ 436.1.

Examples 89 and 90

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamineand 8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and5-(2-bromo-ethyl)-1,2,3-trimethoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 22%, ¹H NMR (DMSO-d₆) δ 8.30 (s, 1H), 7.04 (d, J=9.0 Hz, 1H), 6.88(dd, J=9.0, 3.0 Hz, 1H), 6.58 (d, J=2.9 Hz, 1H), 6.26 (s, 2H), 4.42 (t,J=6.9 Hz, 2H), 3.77 (s, 3H), 3.66 (s, 6H), 3.62 (s, 3H), 3.59 (s, 3H),2.96 (t, J=6.9 Hz, 2H); LC-MS [M+H]⁺ 498.2.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 5%, ¹H NMR (DMSO-d₆) δ 8.36 (s, 1H), 7.26-7.04 (m, 3H), 6.41 (s,2H), 4.56 (t, J=6.8 Hz, 2H), 3.77 (s, 3H), 3.74 (s, 3H), 3.69 (s, 6H),3.61 (s, 3H), 3.09 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 498.2.

Examples 91 and 92

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and5-(2-bromo-ethyl)-1,2,3-trimethoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 23%, ¹H NMR (DMSO-d₆) δ 8.28 (s, 1H), 7.38 (s, 1H), 6.74 (s, 1H),6.27 (s, 2H), 6.19 (s, 2H), 4.40 (t, J=7.4 Hz, 2H), 3.67 (s, 6H), 3.59(s, 3H), 2.96 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 561.10.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 8%, ¹H NMR (DMSO-d₆) δ 8.28 (s, 2H), 7.47 (s, 1H), 7.38 (s, 1H),6.39 (s, 2H), 6.17 (s, 2H), 4.53 (t, J=6.8 Hz, 2H), 3.69 (s, 6H), 3.60(s, 3H), 3.11 (t, J=6.9 Hz, 2H); LC-MS [M+H]⁺ 561.1.

Examples 93 and 94

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and2-(2-bromo-ethyl)-1,3,5-trimethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 23%, ¹H NMR (DMSO-d₆) δ 8.38 (s, 1H), 7.38 (s, 1H), 6.84 (s, 2H),6.76 (s, 1H), 6.09 (s, 2H), 4.25 (t, J=7.8 Hz, 2H), 3.01 (t, J=7.8 Hz,2H), 2.27 (s, 6H), 2.19 (s, 3H); LC-MS [MH]⁺ 513.1.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 10%, ¹H NMR (DMSO-d₆) δ 8.52 (s, 1H), 7.50 (s, 1H), 7.42 (s, 1H),6.82 (s, 2H), 6.20 (s, 2H), 4.28 (t, J=8.4 Hz, 2H), 3.19 (t, J=8.3 Hz,2H), 2.19 (s, 9H); LC-MS [M+H]⁺ 513.1.

Examples 95 and 96

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(1-bromomethyl-cyclobutyl)-4-chloro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-9H-purin-6-ylamine:Yield 16%, ¹H NMR (CD₃OD) δ 8.16 (br s, 1H), 7.26 (d, J=8.8 Hz, 2H),7.14 (s, 1H), 6.95 (d, J=8.9 Hz, 2H), 6.82 (s, 1H) 6.04 (s, 2H), 4.59(s, 2H), 2.77-2.69 (m, 2H), 2.42-2.36 (m, 2H), 2.35-2.26 (m, 1H),1.95-1.85 (m, 1H); LC-MS [M+H]⁺ 545.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-3H-purin-6-ylamine:Yield 7%, ¹H NMR (CD₃OD) δ 7.39 (br s, 1H), 7.29-7.24 (m, 3H), 7.19 (brs, 1H), 6.97-6.92 (m, 2H), 6.09 (s, 2H) 4.69 (s, 2H), 2.58-2.50 (m, 2H),2.44-2.34 (m, 2H), 2.24-2.17 (m, 1H), 1.91-1.82 (m, 1H); LC-MS [M+H]⁺545.0.

Examples 97 and 98

9-[2-(4-Chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-chloro-2-fluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(4-Chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 34%, ¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.30 (dd, J=10.0, 2.1, Hz,1H), 7.16-7.00 (m, 3H), 6.88 (dd, J=8.8, 3.0, Hz, 1H), 6.57 (d, J=2.9Hz, 1H), 4.46 (t, J=6.8 Hz, 2H), 3.74 (s, 3H), 3.62 (s, 3H), 3.10 (t,J=6.8 Hz, 2H); LC-MS [M+H]⁺ 460.1.3-[2-(4-Chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 12%, ¹H NMR (DMSO-d₆) δ 8.39 (s, 1H), 7.40-7.38 (m, 1H), 7.25-7.02(m, 5H), 4.53 (t, J=6.4 Hz, 2H), 3.77 (s, 3H), 3.71 (s, 3H), 3.21 (t,J=6.4 Hz, 2H); LC-MS [M+H]⁺ 460.1.

Examples 99 and 100

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(1-bromomethyl-2-methyl-butyl)-benzene by a procedure similar toexamples 1 and 2.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,a mixture of diastereomers: Yield 19%, ¹H NMR (DMSO-d₆) δ 8.23 (s, 1H),8.21 (s, 1H), 7.36 (s, 2H), 7.15-7.10 (m, 6H), 7.04-6.99 (m, 4H), 6.59(s, 2H), 6.08 (s, 4H), 4.59 (m, 2H), 4.50 (m, 2H), 3.30 (m, 2H), 3.20(m, 2H), 2.45 (m, 4H), 1.05 (d, J=6.4 Hz, 3H), 0.90 (t, J=7.2 Hz, 3H),0.76-0.70 (m, 6H); LC-MS [M+H]⁺ 528.1.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine,a mixture of diastereomers: Yield 3%, ¹H NMR (DMSO-d₆) δ 8.01 (s, 1H),7.99 (s, 1H) 7.48 (s, 2H), 7.39 (s, 2H), 7.24-7.10 (m, 6H), 7.05-7.03(m, 4H), 6.19 (s, 2H), 6.17 (s, 2H), 4.70 (m, 1H), 4.47 (m, 1H), 3.39(m, 2H), 2.45 (m, 2H), 1.78 (m, 2H), 1.24 (m, 2H), 1.01 (d, J=6.4 Hz,3H), 0.85 (t, J=7.6 Hz, 3H), 0.76 (t, J=7.6 Hz, 3H), 0.68 (d, J=6.4 Hz,3H); LC-MS [M+H]⁺ 528.1.

Examples 101 and 102

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclopentyl-2-phenyl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-cyclopentyl-2-phenyl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(2-bromo-1-cyclopentyl-ethyl)-benzene by a procedure similar to examples1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclopentyl-2-phenyl-ethyl)-9H-purin-6-ylamine:Yield 20%, ¹H NMR (DMSO-d₆) δ 8.21 (s, 1H), 7.34 (s, 1H), 7.14-7.06 (m,3H), 6.99 (d, J=8.0 Hz, 2H), 6.57 (s, 1H), 6.08 (bs, 2H), 4.47 (d, J=8.0Hz, 2H), 3.20 (m, 1H), 2.55 (m, 1H), 2.01-1.80 (m, 4H), 1.49-1.30 (m,4H); LC-MS [M+H]⁺ 540.1.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-cyclopentyl-2-phenyl-ethyl)-3H-purin-6-ylamine:Yield 11%, ¹H NMR (DMSO-d₆) δ 7.91 (bs, 1H), 7.48 (bs, 1H), 7.40 (bs,1H), 7.21-7.12 (m, 3H), 7.02 (d, J=7.2 Hz, 2H), 6.16 (s, 1H), 4.65 (dd,J=9.2, 4.4 Hz, 1H), 4.41 (t, J=12 Hz, 1H), 3.21 (m, 2H), 2.43-2.23 (m,1H), 1.99-1.80 (m, 1H), 1.70-1.20 (m, 6H), 0.96-0.91 (m, 1H); LC-MS[M+H]⁺ 540.1.

Examples 103 and 104

9-(2-Cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-(2-cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-1-cyclopentyl-ethyl)-benzene by a procedure similar to examples1 and 2. The isomers were separated by preparative HPLC.9-(2-Cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:Yield 15%, ¹H NMR (DMSO-d₆) δ 8.20 (s, 1H), 7.12-7.06 (m, 3H), 7.01 (d,J=8.8 Hz, 1H), 6.96-6.93 (m, 2H), 6.86 (dd, J=8.8, 2.8 Hz, 1H), 6.45 (d,J=2.4 Hz, 1H), 4.49-4.45 (m, 2H), 3.74 (s, 3H), 3.60 (s, 3H), 3.18-3.01(m, 1H), 2.23-2.22 (m, 1H), 2.00-1.25 (m, 6H), 0.80-0.61 (m, 2H); LC-MS[M+H]⁺ 476.2.3-(2-Cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:Yield 15%, ¹H NMR (DMSO-d₆) δ 7.99 (bs, 1H), 7.24-7.10 (m, 6H), 7.03 (d,J=6.8 Hz, 2H), 4.65 (m, 2H), 3.77 (s, 3H), 3.72 (s, 3H), 2.60-2.40 (m,2H), 2.00-1.25 (m, 8H); LC-MS [M+H]⁺ 476.2.

Examples 105 and 106

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(1-bromomethyl-2-methyl-butyl)-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,a mixture of diastereomers: Yield 25%, ¹H NMR (DMSO-d₆) δ 8.18 (s, 1H),8.16 (s, 1H), 7.24-7.06 (m, 6H), 7.03-6.94 (m, 6H), 6.86-6.84 (m, 2H),6.39 (m, 2H), 4.60-4.45 (m, 2H), 3.75 (s, 6H), 3.59 (s, 6H), 3.50 (m,4H), 2.43 (m, 4H), 0.98 (d, J=6.4 Hz, 6H), 0.90-0.88 (m, 2H), 0.72-0.67(m, 6H); LC-MS [M+H]⁺ 464.2.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine,a mixture of diasereomers: Yield 9%, ¹H NMR (DMSO-d₆) δ 7.99 (s, 2H),7.24-7.10 (m, 10H), 7.06-7.04 (m, 6H), 4.70 (m, 1H), 4.50 (m, 1H), 3.77(s, 6H), 3.74 (m, 2H), 3.73 (s, 6H), 2.45 (m, 4H), 1.02 (d, J=6.4 Hz,3H), 0.88-0.88 (m, 3H), 0.79-0.72 (m, 3H), 0.69 (d, J=6.4 Hz, 3H); LC-MS[M+H]⁺ 464.2.

Examples 107 and 108

2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)ethanoland2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)ethanol

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and2-chloro-1-(2,4-dichloro-phenyl)-ethanol by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)ethanol:Yield 17%, ¹H NMR (DMSO-d₆) δ 10.10 (s, 1H), 7.98 (s, 1H), 7.61 (d,J=8.8 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 6.95 (d, J=3.2 Hz, 1H), 6.87 (d,J=8.8 Hz, 1H), 6.76 (dd, J=8.8, 3.2 Hz, 1H), 6.54 (bs, 2H), 6.42 (bs,1H), 5.54 (t, J=8.8 Hz, 1H), 4.21 (t, J=8.8 Hz, 2H) 3.68 (s, 3H), 3.67(s, 3H); TOF LC-MS [M+H]⁺ 492.0.2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)ethanol:Yield 1.0%, ¹H NMR (DMSO-d₆) δ 8.10 (bs, 1H), 7.63-7.58 (m, 2H), 7.49(dd, J=8.0, 2.4 Hz, 1H), 6.58 (bs, 1H), 6.17 (bs, 2H), 5.63 (m, 1H),4.50 (m, 2H), 3.76 (s, 3H), 3.68 (s, 3H); LC-MS [M+H]⁺ 492.1.

Examples 109 and 110

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-fluoro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 22%, ¹H NMR (DMSO-d₆) δ 8.18 (s, 1H), 7.34 (s, 1H), 7.27-7.21 (m,1H), 7.02-6.97 (m, 1H), 6.93-6.89 (m, 1H), 6.83 (d, J=7.6 Hz, 1H), 6.65(s, 1H), 6.08 (s, 2H), 4.41 (t, J=7.2 Hz, 2H), 3.07 (t, J=7.2 Hz, 2H);LC-MS [M+H]⁺ 490.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:Yield 17%, ¹H NMR (DMSO-d₆) δ 8.10 (bs, 1H), 7.50-7.26 (m, 3H),7.10-7.00 (m, 2H), 6.93 (d, J=7.6 Hz, 1H), 6.16 (bs, 2H), 4.53 (t, J=6.4Hz, 2H), 3.201 (t, J=6.4 Hz, 2H); LC-MS [M+H]⁺ 490.0.

Examples 111 and 112

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-chloro-ethyl)-2-ethoxy-1-methoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.32 (s, 1H), 7.03 (d, J=9.2 Hz, 1H), 6.88 (dd,J=8.8, 2.8 Hz, 1H), 6.76 (d, J=8.4 1H), 6.59-6.56 (m, 2H), 6.48-6.46 (m,1H), 4.42 (t, J=6.8 Hz, 2H) 3.95-3.89 (m, 2H), 3.73 (s, 3H), 3.65 (s,3H), 3.62 (s, 3H), 2.94 (t, J=6.8 Hz, 2H), 1.28 (t, J=6.8 Hz, 2H); LC-MS[M+H]⁺ 482.2.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.32 (s, 1H), 7.24 (d, J=2.8 Hz, 1H), 7.19-7.18 (m,1H), 7.13-7.12 (m, 1H), 6.82 (d, J=8.40 Hz, 1H) 6.72 (d, J=2.0 Hz, 1H),6.56 (dd, J=8.0, 2.0 Hz, 1H), 4.52 (t, J=6.8 Hz, 2H) 3.97-3.92 (m, 2H),3.77 (s, 3H), 3.73 (s, 3H), 3.69 (s, 3H), 3.08 (t, J=6.8 Hz, 2H), 1.29(t, J=6.8 Hz, 3H); LC-MS [M+H]⁺ 482.2.

Examples 113 and 114

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(1-chloromethyl-2-methyl-propyl)-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 7.15-7.07 (m, 3H), 7.03 (d, J=9.2 Hz,1H), 6.98-6.96 (m, 2H), 6.87 (dd, J=6.0, 3.2 Hz, 1H), 6.46 (d, J=2.4 Hz,1H) 4.60-4.47 (m, 1H), 3.74 (s, 3H), 3.60 (s, 3H), 3.17-3.04 (m, 2H),1.99-1.94 (m, 1H), 1.0 (d, J=6.8 Hz, 3H), 0.92 (d, J=6.4 Hz, 3H); LC-MS[M+H]⁺ 450.2.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.06 (s, 1H), 7.23-7.14 (m, 5H), 7.09-7.04 (m, 2H),4.79-4.75 (m, 1H), 4.54-4.48 (m, 2H), 3.8 (s, 3H), 3.74 (s, 3H),3.17-3.13 (m, 1H), 2.0-1.96 (m, 1H), 1.03 (d, J=6.8 Hz, 3H), 0.718 (d,J=6.4 Hz, 3H); LC-MS [M+H]⁺ 450.2.

Examples 115 and 116

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and2-(2-chloro-ethyl)-1,4-dimethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.36 (s, 1H), 7.06-7.01 (m, 2H), 6.93-6.88 (m, 2H),6.71 (s, 1H), 6.59 (d, J=2.8 Hz, 1H), 4.33 (t, J=7.6 Hz, 2H), 3.75 (s,3H), 3.63 (s, 3H), 2.92 (t, J=7.6 Hz, 2H), 2.21 (s, 3H), 2.17 (s, 3H);LC-MS [M+H]⁺ 436.2.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.43 (s, 1H), 7.25 (s, 1H), 7.16 (s, 1H), 7.04 (d,J=8.0 Hz, 2H), 6.96-6.94 (m, 1H), 6.84 (s, 1H), 4.44 (t, J=7.6 Hz, 2H),3.76 (s, 3H), 3.73 (s, 3H), 3.10 (t, J=7.6 Hz, 2H), 2.19 (s, 3H), 2.17(s, 3H); LC-MS [M+H]⁺ 436.2.

Examples 117 and 118

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and4-(2-chloro-ethyl)-2-ethoxy-1-methoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine:LC-MS [M+H]⁺ 546.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.25 (s, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 6.80 (d,J=8.4 Hz, 1H), 6.69 (d, J=1.6 Hz, 1H), 6.55 (dd, J=8.4, 1.6 Hz, 1H),6.17 (s, 2H), 4.51 (t, J=7.2 Hz, 2H), 3.96-3.91 (m, 2H), 3.68 (s, 3H),3.09 (t, J=7.2 Hz, 2H), 1.31-1.27 (m, 3H); LC-MS [M+H]⁺ 546.05.

Examples 119 and 120

9-[2-(4-Chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamineand3-[2-(4-chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-chloro-4-(1-chloromethyl-2-methyl-propyl)-benzene by a proceduresimilar to examples 1 and 2. The isomers were separated by preparativeHPLC.

9-[2-(4-Chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine:¹H NMR (DMSO-d₆) δ 8.25 (s, 1H), 7.16-7.15 (m, 2H), 7.04-6.99 (m, 2H),6.88 (s, 2H), 6.44 (s, 1H), 4.52 (d, J=6.2 Hz, 2H), 3.75 (s, 3H), 3.61(s, 3H), 3.06 (m, 1H), 1.98 (s, 1H), 1.01 (d, J=5.6 Hz, 3H), 0.67 (d,J=6.0 Hz, 3H); LC-MS [M+H]⁺ 484.1.3-[2-(4-Chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine:LC-MS [M+H]⁺ 484.1.

Example 121

9-[2-(2,4-Difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-chloro-ethyl)-2,4-difluoro-benzene by a procedure similar toexamples 1 and 2. The compound was purified by preparative HPLC. LC-MS[M+H]⁺ 444.1.

Examples 122 and 123

9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamineand3-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-chloro-2-(2-chloro-ethyl)-3-fluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine:¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 7.30-7.21 (m, 2H), 7.13-7.08 (m, 1H),7.08 (d, J=3.2 Hz, 1H), 6.86 (dd, J=9.2, 3.2 Hz, 1H), 6.53 (d, J=3.2 Hz,1H), 4.48 (t, J=6.6 Hz, 2H), 3.73 (s, 3H), 3.62 (s, 3H), 3.30 (t, J=6.0Hz, 2H); LC-MS [M+H]⁺ 460.1.3-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine:¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 7.36-7.26 (m, 2H), 7.19-7.15 (m, 3H),7.11-7.09 (m, 1H), 7.57 (t, J=6.4 Hz, 2H), 3.75 (s, 3H), 3.73 (s, 3H),3.34 (t, J=6.0 Hz, 2H); LC-MS [M+H]⁺ 486.1.

Examples 124 and 125

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and2-(2-chloro-ethyl)-1,4-dimethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.30 (s, 1H), 7.37 (s, 1H), 7.01 (d, J=7.6 Hz, 1H),6.84 (d, J=7.6 Hz, 1H), 6.74 (s, 1H), 6.70 (s, 1H), 6.09 (s, 2H), 4.33(t, J=7.6 Hz, 2H), 3.20 (t, J=7.6 Hz, 2H), 2.21 (s, 3H), 2.17 (s, 3H);LC-MS [M+H]⁺ 500.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.43 (s, 1H), 7.50 (s, 1H), 7.41 (s, 1H), 7.04 (d,J=7.6 Hz, 1H), 6.95-6.93 (m, 1H), 6.85 (s, 1H), 6.18 (s, 2H), 4.41 (t,J=7.6 Hz, 2H), 3.12 (t, J=8.0 Hz, 2H), 2.19 (s, 3H), 2.16 (s, 3H); LC-MS[M+H]⁺ 500.0.

Examples 126 and 127

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-chloro-4-(1-chloromethyl-2-methyl-propyl)-benzene by a proceduresimilar to examples 1 and 2. The isomers were separated by preparativeHPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.14 (s, 1H), 7.13-7.07 (m, 3H), 7.00-6.98 (m, 2H),6.56-6.52 (m, 2H), 6.08 (s, 2H), 4.53-4.44 (m, 2H), 3.17-3.13 (m, 1H),1.99-1.97 (m, 1H), 1.04 (d, J=6.8 Hz, 3H), 0.70 (d, J=6.8 Hz, 3H); LC-MS[M+H]⁺ 514.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.0 (s, 1H), 7.39 (s, 1H), 7.24-7.19 (m, 3H),7.18-7.11 (m, 1H), 7.09-7.02 (m, 2H), 6.12 (s, 2H), 4.75-4.71 (m, 1H),4.50-4.43 (m, 1H), 3.25-3.19 (m, 1H), 1.98-1.90 (m, 1H), 1.02 (d, J=6.8Hz, 3H), 0.710 (d, J=6.8 Hz, 3H); LC-MS [M+H]⁺ 514.0.

Examples 128 and 129

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,6-dichloro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,6-dichloro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1,3-dichloro-2-(2-chloro-ethyl)-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,6-dichloro-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.23 (s, 1H), 7.36-7.34 (m, 2H), 7.28-7.24 (m,1H), 7.18 (s, 1H), 6.81 (s, 1H), 6.09 (s, 2H), 4.64 (t, J=6.4 Hz, 2H),3.52 (t, J=6.4 Hz, 2H); LC-MS [M+H]⁺ 539.9.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,6-dichloro-phenyl)-ethyl]-3H-purin-6-ylamine.LC-MS [M+H]⁺ 539.9.

Examples 130 and 131

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-chloro-2-(2-chloro-ethyl)-3-fluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.24 (s, 1H), 7.32-7.27 (m, 1H), 7.22-7.20 (m,2H), 7.07-7.03 (m, 1H), 6.82 (s, 1H), 6.10 (s, 2H), 4.60 (t, J=8.0 Hz,2H), 3.41 (t, J=6.4 Hz, 2H); LC-MS [M+H]⁺ 523.9.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.34 (s, 1H), 7.36-7.29 (m, 2H), 7.26-7.23 (m,2H), 7.09-7.05 (m, 1H), 6.17 (s, 2H), 4.68 (t, J=6.8 Hz, 2H), 3.46 (t,J=6.8 Hz, 2H); LC-MS [M+H]⁺ 523.9.

Examples 132 and 133

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3,5-dimethyl-phenyl)-ethyl]-9H-purine-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,5-dimethyl-phenyl)-ethyl]-3H-purine-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-chloro-ethyl)-3,5-dimethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3,5-dimethyl-phenyl)-ethyl]-9H-purine-6-ylamine:¹H NMR (DMSO-d₆) δ 8.33 (s, 1H), 7.05 (d, J=8.8 Hz, 1H), 6.90 (dd,J=6.0, 3.2 Hz, 1H), 6.60 (d, J=3.2 Hz, 1H), 6.82 (s, 1H), 6.65 (s, 2H),4.37 (t, J=7.2 Hz, 2H), 3.75 (s, 3H), 3.63 (s, 3H), 2.87 (t, J=7.2 Hz,2H), 2.18 (s, 6H); LC-MS [M+H]⁺ 436.2.8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,5-dimethyl-phenyl)-ethyl]-3H-purine-6-ylamine:¹H NMR (DMSO-d₆) δ 8.42 (s, 1H), 7.25 (d, J=2.8 Hz, 1H), 7.19-7.17 (m,1H), 7.11-7.09 (m, 1H), 6.87 (s, 1H), 6.87 (s, 2H), 4.49 (t, J=6.4 Hz,2H), 3.77 (s, 3H), 3.73 (s, 3H), 3.07 (t, J=6.4 Hz, 2H), 2.21 (s, 6H);LC-MS [M+H]⁺ 436.2.

Example 134

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pyridin-4-yl-ethyl)-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-chloro-ethyl)-pyridine by a procedure similar to examples 1 and 2.The compound was purified by preparative HPLC. ¹H NMR (CD₃OD) δ 8.68 (d,J=6.4 Hz, 2H), 8.27 (s, 1H), 7.84 (d, J=6.4 Hz, 2H), 7.06-6.98 (m, 3H),4.75 (t, J=6.8 Hz, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.53 (t, J=6.8 Hz,2H); LC-MS [M+H]⁺ 409.1

Examples 135 and 136

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pyridin-2-yl-ethyl)-9H-purin-6-ylamineand8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-pyridin-2-yl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and2-(2-bromo-ethyl)-pyridine by a procedure similar to example 1 and 2.The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pyridin-2-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.63-8.60 (m, 2H), 8.22 (s, 1H), 8.18 (dt, J=8.0, 2.0Hz, 1H), 7.77 (dd, J=8.0, 2.0 Hz, 1H), 7.07-6.99 (m, 3H), 4.69 (t, J=6.8Hz, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.41 (t, J=6.8 Hz, 2H); TOF LC-MS[M+H]⁺ 409.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-pyridin-2-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.70-8.50 (m, 2H), 8.40 (s, 1H), 8.11 (d, J=7.6 Hz,1H), 7.72 (m, 1H), 7.29 (dd, J=6.8, 1.2 Hz, 1H), 7.23-7.17 (m, 2H), 4.69(t, J=7.2 Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H), 3.41 (t, J=7.2 Hz, 2H);LC-MS [M+H]⁺ 409.1.

Examples 137 and 138

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-iodo-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.23 (s, 1H), 7.56-7.52 (m, 1H), 7.41 (s, 1H),7.04-7.01 (m, 3H), 6.88 (d, J=8.8 Hz, 1H), 6.53 (s, 1H), 4.39 (t, J=6.8Hz, 2H), 3.76 (s, 3H), 3.62 (s, 3H), 2.97 (t, J=6.8 Hz, 2H); LC-MS[M+H]⁺ 534.0.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.21 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.49 (s, 1H),7.30 (s, 1H), 7.20-7.14 (m, 3H), 7.06 (t, J=7.6 Hz, 1H), 4.58 (t, J=7.2Hz, 2H), 3.82 (s, 3H), 3.81 (s, 3H), 3.18 (t, J=7.2 Hz, 2H); LC-MS[M+H]⁺ 534.0.

Examples 139 and 140

8-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-chloro-4-fluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.21 (s, 1H), 7.17 (dd, J=8.8, 2.8 Hz, 1H), 7.08-6.92(m, 5H), 4.59 (t, J=6.8 Hz, 2H), 3.73 (s, 6H), 3.31 (t, J=6.8 Hz, 2H);LC-MS [M+H]⁺ 460.1.3-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.19 (s, 1H), 7.28 (s, 1H), 7.21-7.18 (m, 4H),7.03-6.97 (m, 1H), 4.63 (t, J=6.8 Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H),3.36 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 460.1.

Examples 141 and 142

9-[2-(2-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-bromo-2-(2-bromo-ethyl)-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.9-[2-(2-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d6) δ 8.27 (s, 1H), 7.54 (dd, J=8.0, 1.2 Hz, 1H), 7.22 (t,J=7.2 Hz, 1H), 7.14 (t, J=7.6 Hz, 1H), 7.00 (t, J=7.8 Hz, 1H), 6.99 (d,J=8.8 Hz, 1H), 6.86 (dd, J=8.8, 2.8 Hz, 1H), 6.51 (s, 1H), 4.48 (t,J=6.8 Hz, 2H), 3.72 (s, 3H), 3.61 (s, 3H), 3.18 (t, J=6.8 Hz, 2H); LC-MS[M+H]⁺ 486.1.3-[2-(2-Bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.27 (s, 1H), 7.54 (d, J=7.6 Hz, 1H), 7.30-7.25 (m,2H), 7.19-7.14 (m, 4H), 4.65 (t, J=6.8 Hz, 2H), 3.81 (s, 3H), 3.80 (s,3H), 3.39 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 486.1.

Examples 143 and 144

9-[2-(3,5-Difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3,5-difluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.28 (s, 1H), 7.07-7.03 (m, 3H), 6.81-6.72 (m, 3H),4.58 (t, J=6.8 Hz, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.20 (t, J=6.8 Hz,2H); LC-MS [M+H]⁺ 444.1.3-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.28 (s, 1H), 7.31 (s, 1H), 7.20-7.19 (m, 2H),6.90-6.80 (m, 3H), 4.61 (t, J=7.2 Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H),3.26 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 444.1.

Examples 145 and 146

9-[2-(2,3-Difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2,3-difluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(2,3-Difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.26 (s, 1H), 7.14-7.10 (m, 1H), 7.03-6.98 (m, 4H),6.85-6.81 (m, 1H), 4.61 (t, J=6.8 Hz, 2H), 3.75 (s, 3H), 3.74 (s, 3H),3.30 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 444.1.3-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.24 (s, 1H), 7.29 (dd, J=2.8, 0.8 Hz, 1H), 7.19-7.13(m, 3H), 7.10-7.05 (m, 1H), 6.94 (dt, J=7.6, 1.2 Hz, 1H), 4.64 (t, J=6.8Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H), 3.34 (t, J=6.8 Hz, 2H); LC-MS[M+H]⁺ 444.1.

Examples 147 and 148

8-(6-Bromo-1,3-benzodioxol-5-ylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-fluoro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.17 (s, 1H), 7.33 (s, 1H), 7.25-7.22 (m, 1H),7.11-7.02 (m, 3H), 6.65 (s, 1H), 6.08 (s, 2H), 4.41 (t, J=7.2 Hz, 2H),3.10 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 489.9.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.19 (s, 1H), 7.37 (s, 1H), 7.36 (s, 1H), 7.30-7.22 (m,1H), 7.14-7.00 (m, 3H), 6.16 (s, 2H), 4.62 (t, J=6.8 Hz, 2H), 3.29 (t,J=6.8 Hz, 2H); LC-MS [M+H]⁺ 489.9.

Examples 149 and 150

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-bromo-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-bromo-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-bromo-2-(2-bromo-ethyl)-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-bromo-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.22 (s, 1H), 7.52 (dd, J=8.0, 1.2 Hz, 1H), 7.21-7.11(m, 3H), 7.04 (dd, J=7.8, 1.6 Hz, 1H), 6.95 (s, 1H), 6.06 (s, 2H), 4.60(t, J=6.8 Hz, 2H), 3.31 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 550.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-bromo-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.16 (s, 1H), 7.52 (dd, J=8.0, 1.6 Hz, 1H), 7.37 (s,1H), 7.36 (s, 1H), 7.30-7.23 (m, 1H), 7.17-7.14 (m, 2H), 6.16 (s, 2H),4.64 (t, J=6.8 Hz, 2H), 3.38 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 550.0.

Examples 151 and 152

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyridin-3-yl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyridin-3-yl-ethyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and3-(2-chloro-ethyl)-pyridine by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyridin-3-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.75-7.74 (m, 2H), 8.38 (d, J=8.0 Hz, 1H), 8.27 (s,1H), 7.93 (t, J=8.0 Hz, 1H), 7.26 (s, 1H), 7.15 (s, 1H), 6.09 (s, 2H),4.70 (t, J=6.8 Hz, 2H), 3.49 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 473.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyridin-3-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.65-7.84 (m, 1H), 8.43 (s, 1H), 8.17 (d, J=8.0 Hz,1H), 7.90 (s, 1H), 7.76 (m, 1H), 7.38 (s, 1H), 7.36 (s, 1H), 6.16 (s,2H), 4.70 (t, J=7.2 Hz, 2H), 3.43 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 473.0.

Examples 153 and 154

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-iodo-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.18 (s, 1H), 7.58 (dd, J=7.6, 1.2 Hz, 1H), 7.52 (s,1H), 7.15 (s, 1H), 7.07 (d, J=8.0 Hz, 1H), 7.01 (t, J=7.6, 1.2 Hz, 1H),7.00 (s, 1H), 6.07 (s, 2H), 4.46 (t, J=7.6 Hz, 2H), 3.08 (t, J=7.6 Hz,2H); TOF LC-MS [M+H]⁺ 597.9.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 7.64-7.58 (m, 2H), 7.46 (s, 1H), 7.19 (s, 1H), 7.18 (s,1H), 7.04-6.98 (m, 1H), 6.94-6.89 (m, 1H), 6.08 (s, 2H), 4.48 (t, J=9.2Hz, 2H), 3.18 (t, J=9.2 Hz, 2H); TOF LC-MS [M+H]⁺ 597.9.

Examples 155 and 156

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-methyl-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.27 (s, 1H), 7.24 (s, 1H), 7.15 (d, J=7.2 Hz, 1H),7.11 (dt, J=7.2, 1.2 Hz, 1H), 7.03 (s, 1H), 7.01 (dt, J=7.2, 1.6 Hz,1H), 6.87 (d, J=7.6 Hz, 1H), 6.07 (s, 2H), 4.51 (t, J=7.2 Hz, 2H), 3.20(t, J=7.2 Hz, 2H), 2.37 (s, 3H); TOF LC-MS [M+H]⁺ 486.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.18 (s, 1H), 7.37 (s, 1H), 7.36 (s, 1H), 7.17-7.09 (m,2H), 7.04 (dt, J=7.2, 1.6 Hz, 1H), 6.93 (d, J=7.2 Hz, 1H), 6.16 (s, 2H),4.54 (t, J=7.2 Hz, 2H), 3.23 (t, J=7.2 Hz, 2H), 2.26 (s, 3H); TOF LC-MS[M+H]⁺ 486.0.

Examples 157 and 158

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-naphthalene by a procedure similar to examples 1 and2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.14 (s, 1H), 8.09 (d, J=7.6 Hz, 1H), 7.88 (d, J=8.0Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.58 (dt, J=8.4, 1.6 Hz, 1H), 7.52 (dt,J=8.4, 1.6 Hz, 1H), 7.36 (t, J=8.0 Hz, 1H), 7.22 (d, J=7.6 Hz, 1H), 7.13(s, 1H), 6.95 (s, 1H), 6.06 (s, 2H), 4.62 (t, J=7.2 Hz, 2H), 3.60 (t,J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺ 522.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.33 (s, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.28-7.83(m, 2H), 7.57-7.39 (m, 4H), 7.35-7.32 (m, 2H), 6.13 (s, 2H), 4.73 (t,J=8.0 Hz, 2H), 3.77 (t, J=8.0 Hz, 2H); TOF LC-MS [M+H]⁺ 522.0.

Examples 159 and 160

1-(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanoneand1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-[4-(2-chloro-ethyl)-phenyl]-ethanone by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.1-(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone:¹H NMR (CDCl₃) δ 8.18 (s, 1H), 7.98 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4Hz, 2H), 7.13 (s, 1H), 6.96 (s, 1H), 6.06 (s, 2H), 4.53 (t, J=7.6 Hz,2H), 3.24 (t, J=7.6 Hz, 2H), 2.59 (s, 3H); TOF LC-MS [M+H]⁺ 514.05.1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone:¹H NMR (CDCl₃) δ 7.89 (d, J=8.0 Hz, 2H), 7.61 (s, 1H), 7.25 (s, 1H),7.19 (s, 1H), 7.11 (d, J=8.0 Hz, 2H), 6.11 (s, 2H), 4.54 (t, J=7.2 Hz,2H), 3.30 (t, J=7.2 Hz, 2H), 2.59 (s, 3H); TOF LC-MS [M+H]⁺ 514.05.

Examples 161 and 162

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,3-difluoro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-1,3-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,3-difluoro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2,3-difluoro-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,3-difluoro-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.30 (s, 1H), 7.07 (s, 1H), 7.03 (dt, J=7.6, 1.6 Hz,1H), 6.93-6.90 (m, 1H), 6.80 (s, 1H), 6.70 (dt, J=7.6, 1.6 Hz, 1H), 6.00(s, 2H), 4.50 (t, J=6.8 Hz, 2H), 3.21 (t, J=6.8 Hz, 2H); TOF LC-MS[M+H]⁺ 508.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,3-difluoro-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 7.70 (s, 1H), 7.24 (s, 1H), 7.19 (s, 1H), 7.15-7.07 (m,1H), 7.01-6.95 (m, 1H), 6.63 (dt, J=8.0, 1.6 Hz, 1H), 6.10 (s, 2H), 4.54(t, J=6.8 Hz, 2H), 3.30 (t, J=6.8 Hz, 2H); TOF LC-MS [M+H]⁺ 508.0.

Examples 163 and 164

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-4-methyl-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.16 (s, 1H), 7.14 (s, 1H), 7.09 (d, J=7.6 Hz, 2H),7.00 (d, J=7.6 Hz, 2H), 6.99 (s, 1H), 6.07 (s, 2H), 4.47 (t, J=7.6 Hz,2H), 3.11 (t, J=7.6 Hz, 2H), 2.31 (s, 3H); TOF LC-MS [M+H]⁺ 486.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.26 (s, 1H), 7.40 (s, 1H), 7.33 (s, 1H), 7.09 (d,J=7.6 Hz, 2H), 7.02 (d, J=7.6 Hz, 2H), 6.19 (s, 2H), 4.61 (t, J=7.2 Hz,2H), 3.21 (t, J=7.2 Hz, 2H), 2.27 (s, 3H); TOF LC-MS [M+H]⁺ 486.0.

Examples 165 and 166

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-trifluoromethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.16 (s, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.41 (t, J=7.2Hz, 2H), 7.32 (d, J=7.6 Hz, 1H), 7.15 (s, 1H), 7.04 (s, 1H), 6.08 (s,2H), 4.53 (t, J=7.6 Hz, 2H), 3.23 (t, J=7.6 Hz, 2H); TOF LC-MS [M+H]⁺540.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 7.71 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.43 (t, J=7.6Hz, 1H), 7.38 (s, 1H), 7.25 (s, 1H), 7.20 (s, 1H), 7.18 (d, J=7.6 Hz,1H), 6.10 (s, 2H), 4.53 (t, J=7.2 Hz, 2H), 3.31 (t, J=7.2 Hz, 2H); TOFLC-MS [M+H]⁺ 540.0.

Examples 167 and 168

9-(2-Benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-(2-benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and5-(2-bromo-ethyl)-benzo[1,3]-dioxole by a procedure similar to examples1 and 2. The isomers were separated by preparative HPLC.9-(2-Benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.39 (s, 1H), 7.04 (d, J=8.8 Hz, 1H), 6.94 (dd,J=8.8, 3.2 Hz, 1H), 6.83 (d, J=3.3 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H), 6.68(s, 1H), 6.54 (dd, J=8.0, 1.6 Hz, 1H), 5.94 (s, 2H), 4.54 (t, J=7.2 Hz,2H), 3.79 (s, 3H), 3.71 (s, 3H), 3.08 (t, J=7.2 Hz, 2H); TOF LC-MS[M+H]⁺ 452.1.3-(2-Benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.26 (s, 1H), 7.34 (d, J=2.8 Hz, 1H), 7.22-7.05(m, 2H), 6.74-6.70 (m, 2H), 6.53 (dd, J=8.0, 2.0 Hz, 1H), 5.97 (s, 2H),4.58 (t, J=7.2 Hz, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 3.16 (t, J=7.2 Hz,2H); TOF LC-MS [M+H]⁺ 452.1.

Examples 169 and 170

9-(2-Cyclohexyl-ethyl)-8-(2,5-dimethoxyphenyl-sulfanyl)-9H-purin-6-ylamineand3-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-cyclohexane by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.9-(2-Cyclohexyl-ethyl)-8-(2,5-dimethoxyphenyl-sulfanyl)-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.24 (s, 1H), 6.96 (d, J=9.2 Hz, 1H), 6.84 (dd, J=9.2,2.8 Hz, 1H), 6.80 (d, J=2.8 Hz, 1H), 4.26 (t, J=7.6 Hz, 2H), 3.81 (s,3H), 3.67 (s, 3H), 2.09-2.07 (m, 2H), 1.79-1.70 (m, 1H), 1.68-1.60 (m,4H), 0.99-0.82 (m, 6H); TOF LC-MS [M+H]⁺ 414.2.3-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.04 (s, 1H), 7.20 (d, J=2.8 Hz, 1H), 7.02 (dd, J=9.2,2.8 Hz, 1H), 6.93 (d, J=9.2 Hz, 1H), 4.31 (t, J=7.6 Hz, 2H), 3.794 (s,3H), 3.79 (s, 3H), 1.9-1.6 (m, 3H), 1.38-1.20 (m, 4H), 0.99-0.82 (m,6H); TOF LC-MS [M+H]⁺ 414.2.

Examples 171 and 172

9-(2-Biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamineand3-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and4-(2-bromo-ethyl)-biphenyl by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.9-(2-Biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.19 (s, 1H), 7.58-7.51 (m, 4H), 7.46-7.42 (m, 1H),7.30-7.28 (m, 3H), 7.14 (s, 1H), 6.99 (d, J=2.8 Hz, 2H), 6.04 (s, 2H),4.54 (t, J=7.6 Hz, 2H), 3.20 (t, J=7.6 Hz, 2H); TOF LC-MS [M+H]⁺ 548.0.3-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 7.63 (s, 1H), 7.58-7.51 (m, 4H), 7.46-7.42 (m, 2H),7.39-7.36 (m, 1H), 7.25 (s, 1H), 7.20 (s, 1H), 7.06 (d, J=8.4 Hz, 2H),6.09 (s, 2H), 4.55 (t, J=6.8 Hz, 2H), 3.26 (t, J=6.8 Hz, 2H); TOF LC-MS[M+H]⁺ 548.0.

Examples 173 and 174

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclohexyl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-cyclohexyl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-cyclohexane by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclohexyl-ethyl)-9H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.19 (s, 1H), 7.14 (s, 1H), 7.10 (s, 1H), 6.06 (s, 2H),4.28 (t, J=7.6 Hz, 2H), 1.84-1.60 (m, 7H), 1.30-1.18 (m, 4H), 0.99-0.80(m, 2H); TOF LC-MS [M+H]⁺ 487.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-cyclohexyl-ethyl)-3H-purin-6-ylamine:¹H NMR (CDCl₃) δ 8.03 (s, 1H), 7.22 (s, 1H), 7.17 (s, 1H), 6.08 (s, 2H),4.33 (t, J=7.2 Hz, 2H), 1.84-1.80 (m, 2H), 1.79-1.70 (m, 5H), 1.30-1.18(m, 4H), 0.99-0.80 (m, 2H); TOF LC-MS [M+H]⁺ 487.0.

Examples 175 and 176

4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzenesulfonicacid and4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzenesulfonicacid

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-bromo-ethyl)-benzenesulfonic acid by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzenesulfonicacid: ¹H NMR (DMSO-d6) δ 8.40 (s, 1H), 7.47 (d, J=8.0 Hz, 2H), 7.06 (d,J=9.2 Hz, 1H), 7.01 (d, J=8.0 Hz, 2H), 6.93 (dd, J=9.2, 3.2 Hz, 1H),6.75 (d, J=3.2 Hz, 1H), 4.45 (t, J=7.2 Hz, 2H), 3.73 (s, 3H), 3.65 (s,3H), 3.01 (t, J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺ 488.1.4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzenesulfonicacid: ¹H NMR (DMSO-d6) δ 8.24 (s, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.30 (s,1H), 7.23-7.16 (m, 2H), 7.10 (d, J=8.4 Hz, 2H), 4.59 (t, J=7.2 Hz, 2H),3.79 (s, 3H), 3.77 (s, 3H), 3.21 (t, J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺488.1.

Examples 177 and 178

2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)-ethanoland2-[6-amino-8-(6-bromo-benzo[[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)-ethanol

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and2-chloro-1-(2,4-dichloro-phenyl)-ethanol by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)-ethanol:¹H NMR (Acetone-d₆) δ 8.13 (s, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.43 (d,J=2.0 Hz, 1H), 7.39 (dd, J=8.2, 2.0 Hz, 1H), 7.23 (s, 1H), 7.11 (s, 1H),6.10 (s, 2H), 5.51 (t, J=8.0 Hz, 1H), 4.39 (d, J=8.0 Hz, 2H); TOF LC-MS[M+H]⁺ 555.9.2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)-ethanol:¹H NMR (Acetone-d₆) δ 8.53 (s, 1H), 7.62 (d, J=8.2 Hz, 1H), 7.48 (d,J=2.0 Hz, 1H), 7.39 (dd, J=8.2, 2.0 Hz, 1H), 7.33 (s, 1H), 7.30 (s, 1H),6.22 (s, 2H), 5.51 (dd, 8.4, 3.2 Hz, 1H), 4.74 (dd, J=13.2, 3.2 Hz, 1H),4.37 (dd, J=13.2, 3.2 Hz, 1H); TOF LC-MS [M+H]⁺ 555.9.

Examples 179 and 180

9-(2-Cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-(2-cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-1-cyclohexyl-ethyl)-benzene by a procedure similar to examples1 and 2. The isomers were separated by preparative HPLC.9-(2-Cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.33 (s, 1H), 7.16-7.03 (m, 6H), 6.94 (dd, J=8.8,2.8 Hz, 1H), 6.79 (d, J=2.8 Hz, 1H), 4.75 (dd, J=9.2, 6.0 Hz, 1H), 4.65(dd, J=9.2, 6.0 Hz, 1H), 3.79 (s, 3H), 3.70 (s, 3H), 3.30-3.20 (m, 1H),2.07-2.04 (m, 2H), 1.82-1.78 (m, 1H), 1.64-1.54 (m, 2H), 1.36-1.27 (m,2H), 1.20-1.13 (m, 2H), 0.9-0.84 (m, 2H); LC-MS [M+H]⁺ 490.2.3-(2-cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 7.81 (s, 1H), 7.37 (d, J=2.8 Hz, 1H), 7.26-7.10(m, 7H), 4.92 (dd, J=9.2, 4.4 Hz, 1H), 4.42 (dd, J=9.2, 2.8 Hz, 1H),3.87 (s, 3H), 3.83 (s, 3H), 3.79 (m, 1H), 2.0-1.0 (m, 11H); LC-MS [M+H]⁺490.2.

Examples 181 and 182

9-(2-Biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and4-(2-bromo-ethyl)-biphenyl by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.9-(2-Biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.28 (s, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.56 (d,J=8.4 Hz, 2H), 7.46 (t, J=8.0 Hz, 2H), 7.35 (t, J=8.0 Hz, 1H), 7.23 (d,J=8.8 Hz, 2H), 6.88 (dd, J=8.8, 2.8 Hz, 1H), 6.70 (d, J=2.8 Hz, 1H),4.54 (t, J=7.2 Hz, 2H), 3.82 (s, 3H), 3.64 (s, 3H), 3.15 (t, J=7.2 Hz,2H); TOF LC-MS [M+H]⁺ 484.1.3-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.27 (s, 1H), 7.63 (d, J=8.0 Hz, 2H), 7.59 (d,J=8.4 Hz, 2H), 7.46 (d, J=8.4 Hz, 2H), 7.37 (d, J=7.2 Hz, 1H), 7.35 (t,J=8.0 Hz, 1H), 7.24 (d, J=8.4 Hz, 2H), 7.10 (d, J=9.2 Hz, 1H), 7.06 (dd,J=9.2, 2.8 Hz, 1H), 4.66 (t, J=7.6 Hz, 2H), 3.82 (s, 3H), 3.79 (s, 3H),3.12 (t, J=7.6 Hz, 2H); TOF LC-MS [M+H]⁺ 484.1.

Examples 183 and 184

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-trifluoromethyl-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (Acetone-d₆). δ 8.36 (s, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.52 (t,J=7.6 Hz, 1H), 7.45 (t, J=7.6 Hz, 1H), 7.20 (d, J=7.6 Hz, 1H), 7.02 (d,J=9.2 Hz, 1H), 6.92 (dd, J=9.2, 2.8 Hz, 1H), 6.81 (d, J=2.8 Hz, 1H),4.63 (t, J=7.2 Hz, 2H), 3.78 (s, 3H), 3.70 (s, 3H), 3.37 (t, J=7.2 Hz,2H); TOF LC-MS [M+H]⁺ 476.1.8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.38 (s, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.56 (t,J=7.6 Hz, 1H), 7.48 (t, J=7.6 Hz, 1H), 7.32 (d, J=2.4 Hz, 1H), 7.27 (d,J=7.6 Hz, 1H), 7.13-7.07 (m, 2H), 4.64 (t, J=7.2 Hz, 2H), 3.80 (s, 3H),3.79 (s, 3H), 3.44 (t, J=7.2 Hz, 2H); TOF LC-MS [M+H]⁺ 476.1.

Examples 185 and 186

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and[4-(2-bromo-ethyl)-phenyl]-dimethyl-amine by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (Acetone-d₆). δ 8.43 (s, 1H), 7.13 (d, J=8.8 Hz, 2H), 7.07 (d,J=8.8 Hz, 2H), 7.05 (d, J=8.8 Hz, 1H), 6.97 (dd, J=8.8, 2.8 Hz, 1H),6.90 (d, J=2.8 Hz, 1H), 4.57 (t, J=7.2 Hz, 2H), 3.78 (s, 3H), 3.72 (s,3H), 3.13 (t, J=7.2 Hz, 2H), 3.04 (s, 6H); TOF LC-MS [M+H]⁺ 451.1.8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.27 (s, 1H), 7.13 (dd, J=2.4, 0.8 Hz, 1H),7.20-7.04 (m, 6H), 4.60 (t, J=7.2 Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H),3.20 (t, J=7.2 Hz, 2H), 3.03 (s, 6H); TOF LC-MS [M+H]⁺ 451.1.

Examples 187 and 188

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and[4-(2-bromo-ethyl)-phenyl]-dimethyl-amine by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.45 (s, 1H), 7.25 (s, 1H), 7.13 (d, J=8.8 Hz,2H), 7.05 (d, J=8.8 Hz, 2H), 6.93 (s, 1H), 6.13 (s, 2H), 4.58 (t, J=7.2Hz, 2H), 3.16 (t, J=7.2 Hz, 2H), 3.02 (s, 6H); TOF LC-MS [M+H]⁺ 515.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (Acetone-d₆) δ 8.24 (s, 1H), 7.40 (s, 1H), 7.34 (s, 1H), 6.96 (d,J=8.4 Hz, 2H), 6.71 (d, J=8.4 Hz, 2H), 6.19 (s, 2H), 4.57 (t, J=7.2 Hz,2H), 3.13 (t, J=7.2 Hz, 2H), 2.91 (s, 6H); TOF LC-MS [M+H]⁺ 515.0.

Examples 189 and 190

8-(2,5-Diethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine and8-(2,5-diethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamine and(2-bromo-ethyl)-benzene by a procedure similar to examples 1 and 2. Theisomers were separated by preparative HPLC.8-(2,5-Diethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine: ¹H NMR(CD₃OD) δ 8.25 (s, 1H), 7.26-7.20 (m, 3H), 7.11-7.07 (m, 2H), 7.00-6.96(m, 3H), 4.55 (t, J=7.2 Hz, 2H), 4.00-3.91 (m, 4H), 3.13 (t, J=7.2 Hz,2H), 1.35 (t, J=7.2 Hz, 3H), 1.56 (t, J=6.8 Hz, 3H); LC-MS [M+H]⁺ 436.5.8-(2,5-Diethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine: ¹H NMR(CD₃OD) δ 8.12 (s, 1H), 7.30-7.25 (m, 4H), 7.16-7.15 (m, 2H), 7.11-7.08(m, 2H), 4.61 (t, J=7.2 Hz, 2H), 4.08-4.01 (m, 4H), 3.23 (t, J=7.2 Hz,2H), 1.38 (t, J=7.2 Hz, 3H), 1.21 (t, J=6.8 Hz, 3H); LC-MS [M+H]⁺ 436.5.

Examples 191 and 192

9-[2-(2-Chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-chloro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.9-[2-(2-Chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.25 (s, 1H), 7.35 (dd, J=8.0, 1.2 Hz, 1H), 7.23 (dt,J=7.6, 2.0 Hz, 1H), 7.15 (dt, J=7.6, 1.2 Hz, 1H), 7.05 (dd, J=7.6, 2.0Hz, 1H), 6.96-6.94 (m, 3H), 4.63 (t, J=6.8 Hz, 2H), 3.99-3.91 (m, 4H),3.33 (t, J=6.8 Hz, 2H), 1.35 (t, J=6.4 Hz, 3H), 1.17 (t, J=6.4 Hz, 3H);LC-MS [M+H]⁺ 470.5.3-[2-(2-Chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.11 (s, 1H), 7.36 (dd, J=7.6, 2.0 Hz, 1H), 7.28-7.27(bs, 1H), 7.25-7.20 (m, 2H), 7.18-7.14 (m, 3H), 4.66 (t, J=7.2 Hz, 2H),4.07-4.02 (m, 4H), 3.41 (t, J=7.2 Hz, 2H), 1.38 (t, J=6.0 Hz, 3H), 1.21(t, J=6.0 Hz, 3H); LC-MS [M+H]⁺ 470.5.

Examples 193 and 194

9-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamineand3-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine

The title compounds were prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3,5-dimethoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.9-[2-(3,5-dimethoxy-phenyl-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.33 (s, 1H), 7.03 (d, J=9.0 Hz, 1H), 6.91-6.86 (m,1H), 6.58 (d, J=2.9 Hz, 1H), 6.30 (t, J=1.9 Hz, 1H), 6.17 (d, J=2.2 Hz,2H), 4.42 (t, J=7.0 Hz, 2H), 3.75 (s, 3H), 3.66 (s, 6H), 3.20 (s, 3H),2.95 (t, J=7.0 Hz, 2H); LC-MS [M+H]⁺ 468.1.3-[2-(3,5-dimethoxy-phenyl-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 7.25-7.03 (m, 3H), 6.37 (t, J=2.1 Hz,1H), 6.29 (d, J=2.3 Hz, 2H), 4.55 (t, J=7.1 Hz, 2H), 3.78 (s, 3H), 3.73(s, 3H), 3.69 (s, 6H), 3.10 (t, J=7.1 Hz, 2H); LC-MS [M+H]⁺ 468.1.

Examples 195 and 196

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,5-dimethoxy-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,5-dimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3,5-dimethoxy-benzene by a procedure similar toexamples 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,5-dimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.21 (s, 1H), 7.35 (s, 1H), 6.20 (s, 1H), 6.29 (t,J=2.2 Hz, 1H), 6.18 (d, J=2.2 Hz, 2H), 6.07 (s, 2H), 4.39 (t, J=7.2 Hz,2H), 3.64 (s, 6H), 2.97 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺ 531.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,5-dimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.31 (s, 1H), 7.49 (s, 1H), 7.39 (s, 1H), 6.36 (t,J=2.3 Hz, 1H), 6.27 (d, J=2.2 Hz, 2H), 6.17 (s, 2H), 4.52 (t, J=7.2 Hz,2H), 3.67 (s, 6H), 3.10 (t, J=7.2 Hz, 2H); LC-MS [M+H] 531.0.

Examples 197 and 198

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and3-(2-bromo-ethyl)-thiophene by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.26 (s, 1H), 7.34 (dd, J=1.2, 5.1 Hz, 1H), 7.01 (d,J=9.0 Hz, 1H), 6.92-6.85 (m, 2H), 6.73 (dd, J=3.3, 1.0 Hz, 1H), 6.57 (d,J=3.1 Hz, 1H), 4.41 (t, J=6.8 Hz, 2H), 3.74 (s, 3H), 3.61 (s, 3H), 3.25(t, J=7.4 Hz, 2H); LC-MS [M+H]⁺ 414.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.41 (s, 1H), 7.38 (dd, J=5.1, 1.2 Hz, 1H), 7.26-7.05(m, 3H), 6.96-6.93 (m, 1H), 6.82-6.80 (m, 1H), 4.57 (t, J=7.1 Hz, 2H),3.78 (s, 3H), 3.73 (s, 3H), 3.42 (t, J=6.9 Hz, 2H); LC-MS [M+H]⁺ 414.1.

Examples 199 and 200

8-(2,5-Dimethoxy-phenylsulfanyl)-9-2-thiophen-2-yl-ethyl)-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and2-(2-bromo-ethyl)-thiophene by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.35 (s, 1H), 7.44 (dd, J=4.9, 2.9 Hz, 1H), 7.11-7.02(m, 2H), 6.93-6.83 (m, 2H), 6.62 (d, J=3.0 Hz, 1H), 4.43 (t, J=6.8 Hz,2H), 3.72 (s, 3H), 3.63 (s, 3H), 3.02 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺414.1.8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.37 (s, 1H), 7.51 (dd, J=4.9, 2.7 Hz, 1H), 7.28-7.02(m, 4H), 6.98 (dd, J=4.9, 1.2 Hz, 1H), 4.57 (t, J=6.8 Hz, 2H), 3.78 (s,3H), 3.73 (s, 3H), 3.21 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 414.1.

Examples 201 and 202

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and3-(2-bromo-ethyl)-thiophene by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.26 (s, 1H), 7.38-7.31 (m, 2H), 6.90 (dd, J=5.1, 3.5Hz, 1H), 6.79-6.76 (m, 2H), 6.10 (s, 2H), 4.41 (t, J=6.8 Hz, 2H), 3.29(t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 477.9.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.39 (s, 1H), 7.50 (s, 1H), 7.38-7.35 (m, 2H), 6.95(dd, J=5.1, 3.3 Hz, 1H), 6.81 (dd, J=3.5, 1.2 Hz, 1H), 6.19 (s, 2H),4.55 (t, J=6.8 Hz, 2H), 3.42 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 477.9.

Examples 203 and 204

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-2-yl-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and2-(2-bromo-ethyl)-thiophene by a procedure similar to examples 1 and 2.The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.29 (s, 1H), 7.45 (dd, J=4.9, 2.9 Hz, 1H), 7.39 (s,1H), 7.12 (dd, J=3.0, 1.2 Hz, 1H), 6.89 (dd, J=4.9, 1.4 Hz, 1H), 6.80(s, 1H), 6.10 (s, 2H), 4.40 (t, J=7.2 Hz, 2H), 3.18 (t, J=7.2 Hz, 2H);LC-MS [M+H]⁺ 477.9.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.36 (s, 1H), 7.52-7.48 (m, 2H), 7.39 (s, 1H), 7.18(dd, J=3.0, 1.2 Hz, 1H), 6.98-6.95 (m, 1H), 6.19 (s, 2H), 4.54 (t, J=7.2Hz, 2H), 3.20 (t, J=7.2 Hz, 2H); LC-MS [M+H⁺ 477.9.

Examples 205 and 206

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-nitro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.25 (s, 1H), 8.02-7.97 (m, 1H), 7.92-7.89 (m, 1H),7.48-7.41 (m, 2H), 7.00 (d, J=9.0 Hz, 1H), 6.85 (dd, J=9.0, 3.1 Hz, 1H),6.42 (d, J=3.0 Hz, 1H), 4.53 (t, J=6.9 Hz, 2H), 3.75 (s, 3H), 3.60 (s,3H), 3.21 (t, J=6.9 Hz, 2H); LC-MS [M+H⁺ 453.13.8-(2,5-Dimethoxy-phenylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.43 (s, 1H), 8.14-8.10 (m, 2H), 7.60-7.57 (m, 2H),7.26-7.05 (m, 3H), 4.60 (t, J=6.9 Hz, 2H), 3.78 (s, 3H), 3.74 (s, 3H),3.35 (t, J=6.9 Hz, 2H); LC-MS [M+H]⁺ 453.13.

Examples 207 and 208

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2-nitro-benzene by a procedure similar to examples 1and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.19 (s, 1H), 8.02-7.90 (m, 1H), 7.93-7.91 (m, 1H),7.50-7.40 (m, 2H), 7.29 (s, 1H), 6.53 (s, 1H), 6.18 (s, 2H), 4.49 (t,J=6.9 Hz, 2H), 3.26 (t, J=7.0 Hz, 2H); LC-MS [M+H]⁺ 516.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.41 (s, 1H), 8.12-8.09 (m, 2H), 7.59-7.54 (m, 2H),7.50 (s, 1H), 7.39 (s, 1H), 6.19 (s, 2H), 4.59 (t, J=6.9 Hz, 2H), 3.36(t, J=7.0 Hz, 2H); LC-MS [M+H]⁺ 516.0.

Examples 209 and 210

The title compounds were prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine (J. Comb.Chem., 2001, 3, 518) and (2-bromo-ethyl)-benzene by a procedure similarto example 1 and 2. The isomers were separated by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylmethyl)-9-phenethyl-9H-purin-6-ylamine:Yield 11%, ¹H NMR (DMSO-d6) δ 8.24 (s, 1H), 7.30-7.20 (m, 4H), 7.11-7.09(m, 2H), 6.69 (s, 1H), 6.05 (s, 2H), 4.40-4.34 (m, 2H), 3.97 (s, 2H),3.04-2.98 (m, 2H); LC-MS [M+H]⁺ 452.0.8-(6-Bromo-benzo[1,3]dioxol-5-ylmethyl)-3-phenethyl-3H-purin-6-ylamine:Yield 8%, (CD₃OD) δ 8.19 (s, 1H), 7.26-7.20 (m, 3H), 7.17 (s, 1H),7.11-7.07 (m, 2H), 7.06 (s, 1H), 6.05 (s, 2H), 4.67 (t, J=6.8 Hz, 2H),4.45 (s, 2H), 3.26 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 452.1.

Examples 211 and 212

(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester and(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and[4-(2-bromo-ethyl)-phenyl]-carbamic acid tert-butyl ester by a proceduresimilar to examples 1 and 2. The isomers were separated by preparativeHPLC.(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester: ¹H NMR (DMSO-d₆) δ 9.30 (s, 1H), 8.35 (s, 1H),7.36 (s, 1H), 7.30 (d, J=8.2 Hz, 2H), 6.99 (d, J=8.4 Hz, 2H), 6.71 (s,1H), 6.09 (s, 2H), 4.39 (t, J=6.6 Hz, 2H), 2.99 (t, J=6.8 Hz, 2H), 1.48(s, 9H); LC-MS [M+H]⁺ 586.0.(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester: ¹H NMR (DMSO-d₆) δ 9.30 (s, 1H), 8.29 (s, 1H),7.68-7.31 (m, 4H), 6.99 (d, J=8.4 Hz, 2H), 6.19 (s, 2H), 4.99 (t, J=6.6Hz, 2H), 3.09 (t, J=6.8 Hz, 2H), 1.48 (s, 9H); LC-MS [M+H]⁺ 586.0.

Example 213

9-[2-(4-Amino-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine

To a solution of(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester (0.03 g, 0.04 mmol) in dichloromethane (4.3 mL)was added TFA (0.02 mL, 0.22 mmol) and the reaction mixture was stirredat rt overnight. At the end of this period, reaction was diluted with100 mL of toluene and then concentrated under reduced pressure. Thisprocess was repeated 3 more times to yield the title product (0.03 g,95%) as TFA salt. ¹H NMR (DMSO-d₆) δ 8.19 (s, 1H), 7.24 (s, 1H),7.19-7.02 (m, 4H), 7.00 (s, 1H), 6.13 (s, 2H), 4.45 (t, J=6.8 Hz, 2H),3.18 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 486.3.

Examples 214 and 215

(4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester and(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and[4-(2-bromo-ethyl)-phenyl]-carbamic acid tert-butyl ester by a proceduresimilar to examples 1 and 2. The isomers were separated by preparativeHPLC.(4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester: ¹H NMR (DMSO-d₆) δ 9.28 (s, 1H), 8.28 (s, 1H),7.31 (d, J=8.4 Hz, 2H), 7.03 (d, J=8.4 Hz, 1H), 6.92-6.84 (m, 3H), 6.58(d, J=3.0 Hz, 1H), 4.39 (t, J=6.8 Hz, 2H), 3.74 (s, 3H), 3. 61 (s, 3H),2.91 (t, J=6.8 Hz, 2H), 1.49 (s, 9H); LC-MS [M+H]⁺ 523.22.(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester: ¹H NMR (DMSO-d₆) δ 9.32 (s, 1H), 8.31 (s, 1H),7.38 (d, J=8.4 Hz, 2H), 7.29-7.10 (m, 3H), 7.01 (d, J=8.6 Hz, 2H), 4.50(t, J=6.8 Hz, 2H), 3.79 (s, 3H), 3. 65 (s, 3H), 3.09 (t, J=6.8 Hz, 2H),1.49 (s, 9H); LC-MS [M+H]⁺ 523.2.

Example 216

9-[2-(4-Amino-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine

The title compound was prepared from(4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester by a procedure similar to example 213. ¹H NMR(DMSO-d₆) δ 8.19 (s, 1H), 7.19-6.92 (m, 7H), 4.45 (t, J=6.8 Hz, 2H),3.78 (s, 6H), 3.17 (t, J=6.8 Hz, 2H); LC-MS [M+H]⁺ 423.1.

Example 217

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethoxy-phenyl)-ethyl]-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and.1-(2-bromo-ethyl)-3-trifluoromethoxy-benzene by a procedure similar toexamples 1 and 2. The compound was purified by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethoxy-phenyl)-ethyl]-9H-purin-6-ylamine:Yield 17%, ¹H NMR (CD₃OD) δ 8.18 (s, 1H), 7.33 (t, J=8.0 Hz, 1H),7.12-7.10 (m, 2H), 7.04-7.01 (m, 3H), 6.95 (bs, 1H), 4.57 (t, J=7.2 Hz,2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.24 (t, J=7.2 Hz, 2H); LC-MS [M+H]⁺492.1.

Example 218

8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-2,3,4,5,6-pentafluoro-benzene by a procedure similarto examples 1 and 2. The compound was purified by preparative HPLC.8-(2,5-Dimethoxy-phenylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine.Yield 23%, LC-MS [M+H]⁺ 498.1.

Example 219

9-[2-(3,5-Bistrifluoromethyl-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3,5-bis-trifluoromethyl-benzene by a procedure similarto examples 1 and 2. The compound was purified by preparative HPLC.9-[2-(3,5-Bistrifluoromethyl-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine:¹H NMR (DMSO-d₆) δ 8.10 (s, 1H), 7.86 (s, 1H), 7.54 (s, 2H), 7.01 (d,J=9.0 Hz, 1H), 6.83 (dd, J=11.0, 3.0 Hz, 1H), 6.40 (d, J=2.9 Hz, 1H),4.50 (t, J=7.2 Hz, 2H), 3.75 (s, 3H), 3.59 (s, 3H), 3.24 (t, J=7.2 Hz,2H); LC-MS [M+H]⁺ 544.1.

Example 220

9-[2-(3,5-Bistrifluoromethyl-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3,5-bis-trifluoromethyl-benzene by a procedure similarto examples 1 and 2. The compound was purified by preparative HPLC. ¹HNMR (DMSO-d₆) δ 8.13 (s, 1H), 7.79 (s, 1H), 7.66 (s, 2H), 7.23 (s, 1H),7.01 (s, 1H), 6.09 (s, 2H), 4.59 (t, J=7.4 Hz, 2H), 3.35 (t, J=7.4 Hz,2H); LC-MS [M+H]⁺ 607.0

Example 221

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(-bromomethyl-cyclopropyl)-4-chloro-benzene by a procedure similar toexamples 1 and 2. The compound was purified by preparative HPLC.8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine:¹H NMR (CD₃OD) δ 8.24 (s, 1H), 7.24 (d, J=9.3 Hz, 2H), 7.19 (s, 1H), 714(d, J=8.6 Hz, 2H), 6.93 (s, 1H), 6.08 (s, 2H) 4.49 (s, 2H), 1.41-1.35(m, 2H), 0.95-0.91 (m, 2H); LC-MS [M+H]⁺ 531.8.

Example 222

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-nitro-phenyl)-ethyl]-3H-purin-6-ylamine

The title compound was prepared from8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-nitro-benzene by a procedure similar to examples 1and 2. The compound was purified by preparative HPLC. ¹H NMR (DMSO-d₆) δ8.29 (s, 1H), 7.99-7.95 (m, 1H), 7.56-7.42 (m, 2H), 7.33 (s, 1H),7.10-7.05 (m, 1H), 6.72 (s, 1H), 6.10 (s, 2H), 4.60 (t, J=6.9 Hz, 2H),3.36 (t, J=7.0 Hz, 2H); LC-MS [M+H]⁺ 516.0.

Example 223

8-(2,5-Dimethoxy-phenylsulfanyl)-9-[2-(3-nitro-phenyl)-ethyl]-9H-purin-6-ylamine

The title compound was prepared from8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine and1-(2-bromo-ethyl)-3-nitro-benzene by a procedure similar to examples 1and 2. The compound was purified by preparative HPLC. ¹H NMR (DMSO-d₆) δ8.28 (s, 1H), 7.96 (dd, J=8.0, 1.3 Hz, 1H), 7.53-7.42 (m, 2H), 7.07-7.03(m, 1H), 7.00 (d, J=9.0 Hz, 1H), 6.87 (dd, J=3.1, 9.0 Hz, 1H), 6.53 (d,J=2.8 Hz, 1H), 4.60 (t, J=6.9 Hz, 2H), 3.71 (s, 3H), 3.62 (s, 3H), 3.33(t, J=6.9 Hz, 2H); LC-MS [M+H]⁺ 453.13.

FIG. 2

Example 224

8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-oneStep 1: 6-Chloro-N⁴-phenethyl-pyrimidine-4,5-diamine

To a flask with dichloropyrimidine (2.8 g, 17.0 mmol) in n-BuOH (0.1 M)was added amine (2.3 mL, 18.6 mmol) and TEA (4.7 mL, 33.9 mmol). Theresulting reaction mixture was then heated to 120° C. until startingmaterial was gone as judged by TLC (ca. 4 h). The reaction was thencooled to rt and poured into hexanes at which point a solid formed. Thesolid was filtered off using a fritted funnel and the solid cake washedwith hexanes. The solid (3.8 g, 90% yield) was used without furtherpurification. ¹H NMR (CDCl₃) δ 8.07 (s, 1H), 7.38-7.21 (m, 5H), 5.29(bs, 1H), 3.81 (t, J=7.1 Hz, 2H), 3.60 (bs, 2H), 2.97 (t, J=7.3 Hz, 2H).

Step 2: 9-Phenethyl-1,9-dihydro-purin-6-one

To a flask with chloropyrimidine product above (1.0 g, 4.0 mmol) informamide (0.25 M) was added 2 mL of formic acid. The resulting reactionmixture was then heated to 175° C. for 4 h at which time HPLC showedconsumption of starting material. The reaction was allowed to cool andwater (0.80 M) is added. The resulting solid is filtered off using afritted funnel and the solid cake washed with toluene. The solid (0.6 g,64%) was then used in the next reaction without further purification. ¹HNMR (DMSO-d₆) δ 12.29 (s, 1H), 8.04 (s, 1H), 7.90 (s, 1H), 7.31-7.7.10(m, 5H), 4.39 (t, J=7.0 Hz, 2H), 3.13 (t, J=7.3 Hz, 2H).

Step 3: 8-Bromo-9-phenethyl-1,9-dihydro-purin-6-one

To a solution of purinone from step 2 (0.29 g, 1.21 mmol) from abovereaction in dioxane (0.1M) is added NBS (0.32 g, 1.81 mmol). Theresulting reaction mixture was heated to 105° C. until HPLC showsconsumption of starting material (ca. 2 h). The reaction was cooled tort and purified by MPLC using a solvent gradient of 0-20% MeOH/CH₂Cl₂.The product containing fractions were collected and concentrated toprovide the desired product (0.22 g, 57% yield). ¹H NMR (DMSO-d₆) δ12.49 (s, 1H), 8.08 (s, 1H), 7.30-7.21 (m, 3H), 7.10-7.04 (m, 2H), 4.36(t, J=7.0 Hz, 2H), 3.17 (t, J=7.3 Hz, 2H).

Step 4:8-(Benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one

To a solution of sodium hydride (0.035 g, 0.882 mmol, 60% in mineraloil) in DMF (0.1 M) at 0° C. was added the desired thiophenol (0.140 g,0.882 mmol). The reaction mixture was allowed to warm to rt and mixed 15min at which time the bromo-purinone from step 3 (0.113 g, 0.353 mmol)from the above reaction was added. The resulting reaction mixture wasthen heated to 90° C. overnight. The reaction was then cooled to rt,concentrated, and then purified by MPLC using 0-20% MeOH/CH₂Cl₂. Theproduct containing fractions were collected and concentrated to providethe desired product (0.098 g, 71% yield). ¹H NMR (CDCl₃) δ 12.95 (s,1H), 8.02 (s, 1H), 7.29-6.80 (m, 8H), 5.95 (s, 2H), 4.47 (t, J=7.4 Hz,2H), 3.09 (t, J=7.4 Hz, 2H); LC-MS [M+H]⁺ 393.0.

Example 225

8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one

To a solution of the purine from step 4 (0.088 g, 0.266 mmol) from abovereaction in AcOH (0.2 M) was added bromine (0.02 mL, 0.319 mmol). Theresulting reaction mixture was covered with aluminum foil and allowed tomix at rt until HPLC shows consumption of starting material. Theresulting solution is diluted with 150 mL of toluene and concentrated.This process was repeated two more times and the resulting solid waspurified by preparative HPLC to provide the desired product as a whitesolid (0.059 g, 46% yield). ¹H NMR (DMSO-d₆) δ 12.42 (s, 1H), 8.09 (m,1H), 7.39 (s, 1H), 7.25-7.17 (m, 3H), 7.10-7.04 (m, 2H), 6.81 (s, 1H),6.05 (s, 2H), 4.39 (t, J=7.1 Hz, 2H), 3.03 (t, J=7.1 Hz, 2H); LC-MS[M+H]⁺ 472.3.

Examples 226-336 Examples 226-336 were prepared according to theprocedure described for examples 1 and 2, using appropriate startingmaterials and their names and analytical data is summarized in table 3.All compounds are isolated as trifluoroacetate salts. The skilledartisan readily recognizes that the pendant —N on the purine ringsystems is an amino group (—NH₂) and the pendant —O on the indane ringis a hydroxyl.

TABLE 3 No. Structure Name and analytical data 226

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9- (2-cyclohexyl-2-phenylethyl)-9H-purin-6- amine. ¹H NMR (Acetone d₆) δ 8.19 (s, 1 H), 7.20 (s, 1 H),7.15-7.07 (m, 5 H), 6.63 (s, 1 H), 6.08 (s, 2 H), 4.60-4.50 (m, 3 H),2.50-1.0 (m, 11 H); LC-MS [M + H]⁺ 552.1 227

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3- (2-cyclohexyl-2-phenylethyl)-3H-purin-6- amine. ¹H NMR (Acetone d₆) δ 7.82 (s, 1 H), 7.45 (s,1 H),7.36 (s, 1 H), 7.23-7.17 (m, 3 H), 7.09-7.07 (m, 2 H), 6.20 (s, 2 H),4.95-4.91 (m, 1 H), 4.45-4.43 (m, 1 H), 3.30-3.20 (m, 2 H), 2.60-2.50(m, 3 H), 2.40-1.00 (m, 7 H); LC-MS [M + H]⁺ 552.1 228

8-{[2-Chloro-5- (trifluoromethoxy)phenyl]thio}-9-(2- phenylethyl)-9H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.31 (s, 1 H), 7.65 (d, J = 8.8 Hz, 1H), 7.36-7.30 (m, 2 H), 7.22-7.16 (m, 3 H), 7.08-7.04 (m, 2 H), 4.59 (t,J = 6.8 Hz, 2 H), 3.17 (t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺ 466.0 229

8-{[2-Chloro-5- (trifluoromethoxy)phenyl]thio}-3-(2- phenylethyl)-3H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.08 (s, 1 H), 7.74 (d, J = 8.8 Hz, 1H), 7.71-7.70 (m, 1 H), 7.47-7.44 (m, 1 H), 7.26-7.20 (m, 3 H),7.07-7.03 (m, 2 H), 4.56 (t, J = 6.8 Hz, 2 H), 3.18 (t, J = 6.8 Hz, 2H); LC-MS [M + H]⁺ 466.0 230

8-[(2,5-Dimethoxyphenyl)thio]-2-fluoro-9- (2-phenylethyl)-9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 7.24-7.18 (m, 3 H), 7.05-7.00 (m, 3H), 6.88-6.84 (m, 1 H), 6.49-6.47 (m, 1 H), 4.32 (t, J = 6.8 Hz, 2 H),3.74 (s, 3 H), 3.60 (s, 3 H), 2.95 (t, J = 6.8 Hz, 2 H); TOF- MS [M +H]⁺ 426.2 231

2-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)phenol. ¹H NMR (CD₃OD) δ 7.92 (s, 1 H), 7.30 (s, 1 H),7.20-7.18 (m, 2 H), 7.07-7.02 (m, 1 H), 6.87-6.84 (m, 1 H), 6.72- 6.67(m, 2 H), 4.62 (t, J = 6.2 Hz, 2 H), 3.82 (s, 3 H), 3.80 (s, 3 H), 3.19(t, J = 6.2 Hz, 2 H); TOF-MS [M + H]⁺ 424.1 232

8-(1,3-Benzodioxol-5-ylthio)-9-[2-(2- chlorophenyl)ethyl]-2-fluoro-9H-purin-6- amine. ¹H NMR (DMSO-d₆) δ 7.39 (d, J = 8.0 Hz, 1 H),7.27-7.16 (m, 2 H), 7.03-7.00 (m, 1 H), 6.91 (d, J = 8.0 Hz, 1 H),6.90-6.83 (m, 2 H), 6.04 (s, 2 H), 4.37 (t, J = 6.8 Hz, 2 H), 3.13 (t, J= 6.8 Hz, 2 H); LC-MS [M + Na]⁺ 469.2 233

8-[(7-Bromo-2,3-dihydro-1,4-benzodioxin-6-yl)thio]-9-[2-(2-chlorophenyl)ethyl]-9 H- purin-6-amine. ¹H NMR (CD₃OD)δ 8.14 (s, 1 H), 7.38-7.34 (m, 1 H), 7.23-7.14 (m, 3 H), 7.04-7.00 (m, 1H), 6.92 (s, 1 H), 4.90-4.80 (m, 2 H), 4.60-4.50 (m, 4 H), 4.28-4.22 (m,2 H); TOF-MS [M + H]⁺ 518.0 234

8-[(7-Bromo-2,3-dihydro-1,4-benzodioxin-6-yl)thio]-3-[2-(2-chlorophenyl)ethyl]-3 H- purin-6-amine. ¹H NMR (CD₃OD)δ 8.47 (s, 1 H), 7.40-7.30 (m, 1 H), 7.23-7.05 (m, 3 H) 7.19 (s, 1 H),7.12 (s, 1 H), 4.90-4.80 (m, 4 H), 4.28-4.26 (m, 2 H), 1.80-1.60 (m, 2H); TOF-MS [M + H]⁺ 518.0 235

2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]- 9 H-purin-9-yl}indan-1-ol. ¹HNMR (DMSO- d₆) δ 8.14 (s, 1 H), 7.29-7.21 (m, 2 H), 7.10- 7.05 (m, 1 H),7.00-6.98 (m, 1 H), 6.90-6.87 (m, 1 H), 6.75-6.74 (m, 1 H), 6.03-6.02(m, 1 H), 5.28-5.25 (m, 1 H), 3.65 (s, 3 H), 3.54 (s, 3 H), 3.40-3.33(m, 1 H), 2.90-2.80 (m, 2 H); TOF-MS [M + H]⁺ 436.1 236

2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]- 3 H-purin-3-yl}indan-1-ol. ¹HNMR (DMSO- d₆) δ 8.27 (s, 1 H), 7.32-7.30 (m, 2 H), 7.20- 7.10 (m, 3 H),7.02-6.99 (m, 2 H), 5.97-5.95 (m, 1 H), 3.72 (s, 3 H), 3.69 (s, 3 H),3.70-3.30 (m, 1 H), 2.90-2.80 (m, 2 H); TOF-MS [M + H]⁺ 436.1 237

9-[2-(2-Chlorophenyl)ethyl]-2-fluoro-8- [(3,4,5-trimethoxyphenyl)thio]-9H-purin-6- amine. ¹H NMR (CD₃OD) δ 7.34 (dd, J = 8.0, 1.6 Hz. 1 H), 7.21(dt, J = 8.0, 1.6 Hz. 1 H), 7.14 (dt, J = 8.0, 1.6 Hz, 1 H), 6.98 (dd, J= 8.0, 1.6 Hz, 1 H), 6.70 (s, 2 H), 4.46 (t, J = 6.8 Hz, 2 H), 3.78 (s,6 H), 3.48 (s, 3 H), 3.25 (t, J = 6.8 Hz, # 2 H); LC-MS [M + H]⁺ 490.3238

9-[2-(2-Chlorophenyl)ethyl]-8-[(2-chloro-3,4,5-trimethoxyphenyl)thio]-2-fluoro-9 H- purin-6-amine. TOF-MS [M +H]⁺ 522.0 239

8-[(2-Chloro-3,4,5-trimethoxyphenyl)thio]-9-[2-(2,6-dichlorophenyl)ethyl]-2-fluoro-9 H- purin-6-amine. TOF-MS [M +H]⁺ 558.0 240

8-[(3-Chloro-4-methoxyphenyl)thio]-9-(2- phenylethyl)-9 H-purin-6-amine.¹H NMR (CD₃OD) δ 7.87-7.84 (m, 1 H), 7.79-7.72 (m, 1 H), 7.65-7.61 (m, 1H), 7.58-7.43 (m, 2 H), 7.32-7.26 (m, 1 H), 7.08-6.97 (m, 2 H), 6.15-6.11 (m, 1 H), 4.67-4.50 (m, 2 H), 1.60 (s, 3 H), 1.40-1.20 (m, 2 H);TOF-MS [M + H]⁻ 410.4 241

8-[(3-Chloro-4-methoxyphenyl)thio]-3-(2- phenylethyl)-3 H-purin-6-amine.TOF-MS [M + H]⁺ 412.3 242

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(2-chlorophenyl)ethyl]-2-fluoro-9 H-purin- 6-amine. ¹H NMR (DMSO-d₆)δ 7.38-7.34 (m, 1 H), 7.31 (s, 1 H), 7.24-7.16 (m, 2 H), 7.06-7.0 (m, 1H), 6.59 (s, 1 H), 6.07 (s, 2 H), 4.40-4.36 (m, 2 H), 3.20-3.10 (m, 2H); TOF-MS [M + H]⁺ 522.9 243

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(undecafluorocyclohexyl)ethyl]-9 H-purin- 6-amine. TOF-MS [M + H]⁺673.8 244

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(undecafluorocyclohexyl)ethyl]-3 H-purin- 6-amine. TOF-MS [M + H]⁺673.8 245

8-[(2,5-Dimethoxyphenyl)thio]-9-[2- (undecafluorocyclohexyl)ethyl]-9H-purin-6- amine. ¹H NMR (Acetone-d₆) δ 8.65 (s, 1 H), 7.27 (s, 1 H),7.07-7.02 (m, 2 H), 4.82-4.77 (m, 2 H), 3.81- 3.70 (m, 2 H) 3.78 (s, 3H), 3.75 (s, 3 H); TOF- MS [M + H]⁺ 612.0 246

8-[(2,5-Dimethoxyphenyl)thio]-3-[2- (undecafluorocyclohexyl)ethyl]-3H-purin-6- amine. ¹H NMR (Acetone-d₆) δ 8.38 (s, 1 H), 7.08-7.05 (m, 1H), 6.98-6.94 (m, 1 H), 6.87- 6.86 (m, 1 H), 4.72 (t, J = 8.4 Hz, 2 H),3.80 (s, 3 H), 3.71 (s, 3 H), 2.95 (d, J = 8.4 Hz, 2 H); TOF-MS [M + H]⁺612.0 247

8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(4- methoxyphenyl)ethyl]-9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.22 (s, 1 H), 7.62 (s, 1 H), 7.02(d, J = 8.8 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 2 H), 6.86 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 7.6 Hz, 1 H), 4.35 (t, J = 7.2 Hz, 2 H), 3.75 (s, 3 H),3.69 (s, 3 H), 3.60 (s, 3 H), 2.92 (t, # J = 7.2 Hz, 2 H); LC-MS [M +H]⁺ 438.1 248

9-[2-(4-Chlorophenyl)ethyl]-8-[(2,5- dimethoxyphenyl)thio[-9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.25 (s, 1 H), 7.27 (d, J = 7.6 Hz,2 H), 7.05-7.01 (m, 2 H), 6.87 (d, J = 9.2 Hz, 2 H), 6.52 (s, 1 H), 4.42(t, J = 7.2 Hz, 2 H), 3.74 (s, 3 H), 3.62 (s, 3 H), 3.02 (t, J = 7.2 Hz,2 H); LC-MS [M + H]⁺ 442.1 249

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9- [2-(4-fluorophenyl)ethyl]-9H-purin-6- amine. LC-MS [M + H]⁺ 488.0 250

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(4-methoxyphenyl)ethyl]-9H-purin-6- amine. LC-MS [M + H]⁺ 500.0 251

9-[2-(2,6-Dichlorophenyl)ethyl]-8-[(2,5- dimethoxyphenyl)thio]-9H-purin-6- amine. LC-MS [M + H]⁺ 476.1 252

8-{[3-(Difluoromethoxy)phenyl]thio}-9-(2- phenylethyl)-9 H-purin-6-amine¹H NMR (DMSO-d₆) δ 8.30 (s, 1 H), 7.40 (s, 1 H), 7.30-7.10 (m, 8 H),4.50 (t, J = 7.2 Hz, 2 H), 3.10 (t, J = 7.2 Hz, 2 H), 1.30 (s, 1 H);LC-MS [M + H]⁺ 414.4 253

9-[2-(2,6-Dichlorophenyl)ethyl]-8-{[3- (difluoromethoxy)phenyl]thio }-9H-purin-6- amine. LC-MS [M + H]⁺ 482.0 254

9-[2-(2-Chloro-6-fluorophenyl)ethyl]-8-{[3-(difluoromethoxy)phenyl]thio}-9 H-purin-6- amine. LC-MS [M + H]⁺ 466.1255

8-[(4-Chloro-2,5-dimethoxyphenyl)thio]-9-[2-(2,6-dichlorophenyl)ethyl]-9H-purin-6- amine. LC-MS [M + H]⁺ 512.0256

8-[(4-Chloro-2,5-dimethoxyphenyl)thio]-9-[2-(2-chloro-6-fluorophenyl)ethyl]-9 H-purin- 6-amine ¹H NMR (DMSO-d₆) δ8.15 (s, 1 H), 7.25- 7.20 (m, 5 H), 4.50 (t, J = 6.0 Hz, 2 H) 3.73 (s, 3H), 3.67 (s, 3 H), 3.25-3.20 (m, 2 H); LC- MS [M + H]⁺ 494.0 257

8-[(4-Chloro-2,5-dimethoxyphenyl)thio]-9- (2-phenylethyl)-9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.25 (s, 1 H), 7.30- 7.20 (m, 4 H),7.10-7.00 (m, 3 H), 4.50 (t, J = 6.8 Hz, 2 H), 3.73 (s, 3 H), 3.70 (s, 3H), 3.00 (t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺ 442.1 258

9-[2-(2-Chlorophenyl)ethyl]-8-{[3- (difluoromethoxy)phenyl]thio}-9H-purin-6- amine. LC-MS [M + H]⁺ 448.0 259

9-(2-Phenylethyl)-8-[(2,4,5- trichlorophenyl)thio]-9 H-purin-6-amine ¹HNMR (DMSO-d₆) δ 8.30 (s, 1 H), 7.97 (s, 1 H), 7.22 (s, 1 H), 7.17-7.00(m, 3 H), 7.00- 6.98 (m, 2H), 4.50 (t, J = 6.8 Hz, 2 H), 3.00 (t, J =6.8 Hz, 2 H); LC-MS [M + H]⁺ 450.4 260

8-[(4-Chloro-2,5-dimethoxyphenyl)thio]-9-[2-(2-chlorophenyl)ethyl]-9H-purin-6-amine ¹H NMR (Acetone-d₆) δ 8.20(s, 1 H), 7.36- 7.29 (m, 1 H), 7.23-7.13 (m, 2 H), 7.13 (s, 1 H),7.07-7.04 (m, 1 H), 6.98 (s, 1 H), 4.57 (t, J = 7.2 Hz, 2 H), 3.83 (s, 3H), 3.72 (s, 3 H), 3.28 (t, J = 7.2 Hz, 2 H); LC-MS [M + H]⁺ 476.0 261

9-[2-(2-Chlorophenyl)ethyl]-8-[(2-iodo-4,5- dimethoxyphenyl)thio]-9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.23 (s, 1 H), 7.40 - 7.37 (m, 2 H),7.26-7.17 (m, 2 H), 7.10-7.06 (m, 1 H), 6.89 (s, 1 H), 4.50 (t, J = 6.8Hz, 2 H), 3.77 (s, 3 H), 3.61 (s, 3 H), 3.20 (t, J = 6.8 Hz, 2 H); LC-MS[M + H]⁺ 568.3 262

9-[2-(2-Chlorophenyl)ethyl]-8-[(2,4,5- trichlorophenyl)thio]-9H-purin-6-amine. LC-MS [M + H]⁺ 484.2 263

9-[2-(2-Chloro-6-fluorophenyl)ethyl]-8- [(2,4,5-trichlorophenyl)thio]-9H-purin-6- amine. LC-MS [M + H]⁺ 502.9 264

8-[(2,5-Dimethoxyphenyl)thio]-3-(4- nitrobenzyl)-3 H-purin-6-amine. ¹HNMR (DMSO-d₆) δ 8.60 (s, 1 H), 8.21-8.18 (m, 2 H), 7.65-7.62 (m, 2 H),6.94-6.92 (m, 1 H), 6.91-6.89 (m, 1 H), 6.76-6.73 (m, 1 H), 5.60 (s, 2H), 3.70 (s, 3 H), 3.60 (s, 3 H); LC- MS [M + H]⁺ 439.1 265

3-Benzyl-8-[(6-bromo-1,3-benzodioxol-5- yl)thio]-3 H-purin-6-amine. ¹HNMR (DMSO-d₆) δ 8.80 (s, 1 H), 7.50- 7.45 (m, 3 H), 7.40-7.30 (m, 4 H),6.20 (s, 2 H), 5.50 (s, 2 H); LC-MS [M + H]⁺ 457.9 266

8-[(2,5-Dimethoxyphenyl)thio]-9-(4- fluorobenzyl)-9 H-purin-6-amine. ¹HNMR (DMSO-d₆) δ 8.20 (s, 1 H), 7.23- 7.20 (m, 2 H), 6.97-6.95 (m, 2 H),6.82-6.70 (m, 2 H), 6.33 (d, J = 2.8 Hz, 1 H), 5.40 (s, 2 H), 3.70 (s, 3H), 3.60 (s, 3 H); LC-MS [M + H]⁺ 412.1 267

N-(4-{[6-Amino-9-(2-phenylethyl)-9 H- purin-8-yl]thio}-2-hydroxyphenyl)formamide. ¹H-NMR (DMSO-d₆) δ 10.52 (s, 1 H), 9.72 (s, 1H), 8.38 (d, J = 11.7, 1.9 Hz, 2 H), 7.58-7.48 (broad s, 1 H), 7.30-7.19(m, 3 H), 7.10-7.05 (m, 2 H), 4.35 (t, J = 7.2 Hz, 2 H), 2.93 (t, J =7.2 Hz, 2 H); TOF-MS [M + H]⁺ 407.1 268

N-(4-{[6-Amino-3-(2-phenylethyl)-3 H- purin-8-yl]thio}-2-hydroxyphenyl)formamide. TOF-MS [M + H]⁺ 407.1 269

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)quinazolin-4(3 H)-one ¹H-NMR (DMSO-d₆) δ 8.06-8.00 (m, 2 H),7.98 (s, 1 H), 7.79 (dt, J = 7.1, 1.5 Hz, 1 H), 7.67 (d, H = 7.6 Hz, 1H), 7.53-7.47 (m, 1 H), 7.20 (s, 1 H), 6.51 (s, 1 H), 6.60 (s, 2H ),4.65- 4.60 (m, 2 H), 4.44-4.39 (m, 2 H); # LC-MS [M + H]⁺ 538.3 270

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)quinazolin-4(3 H)-one LC-MS [M + H]⁺ 538.3 271

3-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)quinazolin-4(3 H)-one ¹H-NMR (DMSO-d₆) δ 8.07-8.01 (m, 2 H),7.94 (s, 1 H), 7.82-7.77 (m, 1 H), 7.59 (d, J = 8.2 Hz, 1 H), 7.54-7.48(m, 1 H), 6.95 (d, J = 9.1 Hz, 1 H), 6.80 (dd, J = 9.0, 2.9 Hz, 1 H),6.53 (d, J = 2.9 Hz, 1 H), 4.66-4.60 (m, 2 H), # 4.42-4.36 (m, 2 H),3.69 (s, 3 H), 3.61 (s, 3 H); LC-MS [M + H]⁺ 476.4 272

3-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-3 H-purin-3-yl}ethyl)quinazolin-4(3 H)-one LC-MS [M + H]⁺ 476.4 273

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)- N-(tert-butyl)benzenesulfonamide. ¹H-NMR (DMSO-d₆)δ 8.27 (s, 1 H), 7.68 (d, J = 8.4 Hz, 2 H), 7.38 (s, 1 H), 7.24 (d, J =8.4 Hz, 2 H), 7.00 (s, 2 H), 6.85 (s, 1 H), 4.49 (t, J = 6.8 Hz, 2 H),3.16 (t, J = 6.8 Hz, 2 H), 1.04 (s, 9 H); LC-MS # [M + H]⁺ 605.4 274

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl) N-(tert-butyl)benzenesulfonamide. LC-MS [M + H]⁺605.4 275

4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)-N-(tert-butyl)benzenesulfonamide. ¹H NMR (DMSO-d₆) δ 8.24 (s,1 H), 7.66 (d, J = 8.2 Hz, 2 H), 7.20 (d, J = 8.2 Hz, 2 H), 7.03 (d, J =9.0 Hz, 1 H), 6.90 (dd, J = 9.0, 3.1 Hz, 1 H), 6.58 (d, J = 2.9 Hz, 1H), 4.50- 4.42 (m, 2 H), 3.73 (s, 3 H), 3.63 (s, 3 H), # 3.20-3.08 (m, 2H), 1.05 (s, 9 H); LC-MS [M + H]⁺ 543.5 276

4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-3 H-purin-3-yl}ethyl)-N-(tert-butyl)benzenesulfonamide. LC-MS [M + H]⁺ 543.5 277

N-[4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)phenyl]-N′-butylurea. ¹H-NMR (DMSO-d₆) δ 8.35 (s, 1 H), 8.31(s, 1 H), 7.25 (d, J = 8.6 Hz, 2 H), 7.03 (d, J = 9.0 Hz, 1 H),6.91-6.84 (m, 2 H), 6.59 (d, J = 2.9 Hz, 1 H), 6.12-6.08 (m, 1 H), 4.37(t, J = 8.0 Hz, 2 H), 3.75 (s, 3 H), 3.12 (s, 3 H), 3.05 (q, # J = 6.5Hz, 2 H), 2.90 (t, J = 8.0 Hz, 2 H), 1.42- 1.25 (m, 4 H), 0.89 (t, J =7.23 Hz, 3 H); LC-MS [M + H]⁺ 522.5 278

N-[4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-3 H-purin-3-yl}ethyl)phenyl]-N′-butylurea. LC-MS [M + H]⁺ 522.5 279

9-{[1-(4-Chlorophenyl)cyclopropyl]methyl}-8-[(2,5-dimethoxyphenyl)thio]-9 H-purin-6- amine. ¹H NMR (DMSO-d₆) δ8.15 (s, 1 H), 7.21 (d, J = 8.4 Hz, 2 H), 7.05 (d, J = 8.4 Hz, 2 H),6.94 (d, J = 9.0 Hz, 1 H), 6.81 (dd, J = 9.0, 3.1 Hz, 1 H), 6.42 (d, J =2.9 Hz, 1 H), 4.40 (s, 2 H), 3.69 (s, 3 H), 3.60 (s, 3 H), 1.30- # 1.25(m, 2 H), 0.80-0.75 (m, 2 H); TOF-MS [M + H]⁺ 468.1 280

3-{[1-(4-Chlorophenyl)cyclopropyl]methyl}-8-](2,5-dimethoxyphenyl)thio]-3 H-purin-6- amine. TOF-MS [M + H]⁺ 468.1281

N-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)phenyl]-N′-butylurea. ¹H NMR (DMSO-d₆) δ 8.24 (s, 1 H), 7.35(s, 1 H), 7.24 (d, J = 8.4 Hz, 2 H), 6.90 (d, J = 8.40 Hz, 2 H), 6.71(s, 1 H), 6.18 (s, 2 H), 4.35 (t, J = 7.4 Hz, 2 H), 3.05 (q, J = 6.6 Hz,2 H), 2.93 (t, J = 7.2 Hz, 2 H), # 1.42-1.25 (m, 4 H), 0.89 (t, J = 7.2Hz, 3 H); LC-MS [M + H]⁺ 584.5 282

9-[2-(2-Aminophenyl)ethyl]-8-[(6-bromo- 1,3-benzodioxol-5-yl)thio]-9H-purin-6- amine. ¹H NMR (DMSO-d₆) δ 8.30 (s, 1 H), 7.38 (s, 1 H),7.19-7.13 (m, 1 H), 6.84-6.70 (m, 4 H), 6.10 (s, 2 H), 4.39 (t, J = 7.6Hz, 2 H), 2.99 (t, J = 7.6 Hz, 2 H); TOF-MS [M + H]⁺ 485.04 283

8-(1,3-Benzoxazol-6-ylthio)-9-(2- phenylethyl)-9 H-purin-6-amine. ¹H-NMR (DMSO-d₆) δ 8.82 (s, 1 H), 8.18 (s, 1 H), 7.83 (d, J = 1.7 Hz, 1 H),7.79 (d, J = 8.6 Hz, 1 H), 7.42-7.15 (m, 3 H), 7.26-7.16 (m, 3 H), 4.42(t, J = 7.6 Hz, 2 H), 3.00 (t, J = 7.0 Hz, 2 H); TOF-MS [M + H]⁺ 389.12284

8-(1,3-Benzoxazol-6-ylthio)-3-(2- phenylethyl)-3 H-purin-6-amine. TOF-MS[M + H]⁺ 389.12 285

8-[(2,5-Dimethoxyphenyl)thio]-9-(2- phenylbutyl)-9 H-purin-6-amine. ¹HNMR (DMSO-d₆) δ 8.28 (s, 1 H), 7.25- 7.14 (m, 3 H), 7.08-7.01 (m, 3 H),6.87 (dd, J = 9.0, 3.1 Hz, 1 H), 6.51 (d, J = 2.9 Hz, 1 H), 4.45-4.30(m, 2 H), 3.75 (s, 3 H), 3.60 (s, 3 H), 3.15-3.05 (m, 1 H), 1.70-1.55(m, 2 H), 0.65 (t, J = 7.4 Hz, 3 H); TOF-MS # [M + H]⁺ 436.1 286

8-[(2-Chloro-3,4,5 -trimethoxyphenyl)thio]- 9-(2-phenylethyl)-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.19 (s, 1 H), 7.90-7.26 (m, 3 H),7.10-7.07 (m, 2 H), 6.94 (s, 1 H), 4.52 (t, J = 6.8 Hz, 2 H), 3.87 (s, 6H), 3.78 (s, 3 H), 3.13 (t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺ 472.4 287

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9- [2-(2-methoxyphenyl)ethyl]-9H-purin-6- amine. ¹H NMR (CD₃OD) δ 8.23 (s, 1 H), 7.23-7.17 (m, 2 H),6.97 (s, 1 H), 6.90-6.85 (m, 2 H), 6.76 (dd, J = 7.6, 0.8 Hz, 1 H), 6.06(s, 2 H), 4.55 (t, J = 6.8 Hz, 2 H), 3.72 (s, 3 H), 3.19 (t, J = 6.8 Hz,2 H); TOF-MS [M + H]⁺ 500.03 288

8-[(3-Methoxyphenyl)thio]-3-(2- phenylethyl)-3 H-purin-6-amine. ¹H NMR(CD₃OD) δ 7.74 (s, 1 H), 7.32-7.17 (m, 4 H), 7.13-7.05 (m, 4 H), 6.91(m, 1 H), 4.53 (t, J = 6.8 Hz, 2 H), 3.78 (s, 3 H), 3.20 (t, J = 6.8 Hz,2 H); TOF-MS [M + H]⁺ 378.18 289

8-(1,3-Benzodioxol-5-ylthio)-9-[2-(2- chlorophenyl)ethyl]-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.11 (s, 1 H), 7.39-7.32 (m, 2 H),7.26-7.19 (m, 1 H), 7.16-7.11 (m, 1 H), 6.99-6.94 (m, 1 H), 6.87-6.80(m, 2 H), 6.00 (s, 2 H), 4.50 (t, J = 6.4 Hz, 2 H), 3.33-3.25 (m, 2 H);LC-MS [M + H]⁺ 426.1 290

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-2{2-[2-(trifluoromethyl)phenyl]ethyl}-9 H- 1 H), 7.70 (d, J = 7.2 Hz, 1H) 7.50-7.40 (m, purin-6-amine. ¹H NMR (CD₃OD) δ 8.26 (s, 7.04 (s, 1 H),6.07 (s, 2 H), 4.59 (t, J = 6.8 Hz, 2 H), 3.38 (t, J = 6.8 Hz, 2 H);TOF-MS [M + H]⁺ 538.01 291

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-2{2-[2-(trifluoromethyl)phenyl]ethyl}-3 H- purin-6-amine. ¹H NMR (CD₃OD)δ 8.24 (s, 1 H), 7.68 (d, J = 7.6 Hz, 1 H), 7.53 (t, J = 7.2 Hz, 1 H),7.44 (t, J = 7.6 Hz, 1 H), 7.36 (s, 1 H), 7.34 (s, 1 H), 7.3 (d, J =7.6Hz, 1 H), 6.15 (s, 2 H), 4.62 (t, J = 6.8 Hz, 2 H), 3.41 (t, # J = 6.8Hz, 2 H); TOF-MS [M + H]⁺ 538.01 292

8-[(2,2-Difluoro-1,3-benzodioxol-5-yl)thio]- 9-(2-phenylethyl)-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.27 (s, 1 H), 7.40-7.20 (m, 6 H),7.10-7.04 (m, 2 H), 4.54 (t, J = 6.8 Hz, 2 H), 3.18 (t, J = 6.8 Hz, 2H); TOF-MS [M + H]⁺ 428.1 293

8-[(2,2-Difluoro-1,3-benzodioxol-5-yl)thio]- 3-(2-phenylethyl)-3H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.11 (s, 1 H), 7.70 (d, J = 2.0 Hz, 1H), 7.61 (dd, J = 8.4, 1.6 Hz, 1 H), 7.42 (d, J = 8.4 Hz, 1 H),7.29-7.22 (m, 3 H), 7.11-7.07 (m, 2 H), 4.58 (t, J = 7.2 Hz, 2 H), 3.20(t, J = 7.2 Hz, 2 H); TOF-MS [M + H]⁺ 428.1 294

9-[2-(2-Chlorophenyl)ethyl]-8-[(2,2-difluoro-1,3-benzodioxol-5-yl)thio]-9 H- purin-6-amine. ¹H NMR (CD₃OD) δ8.11 (s, 1 H), 7.40-7.27 (m, 4 H), 7.23 (dt, J = 7.6, 1.6 Hz, 1 H), 7.16(dt, J = 7.6, 1.6 Hz, 1 H), 7.04 (dd, J = 7.6, 1.6 Hz, 1 H), 4.60 (t, J= 6.8 Hz, 2 H), 3.34 (t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 462.0 295

3-[2-(2-Chlorophenyl)ethyl]-8-[(2,2-difluoro-1,3-benzodioxol-5-yl)thio]-3 H- purin-6-amine. ¹H NMR (CD₃OD) δ8.93 (s, 1 H), 8.55 (d, J = 2.0 Hz, 1 H), 8.28-8.19 (m, 3 H), 8.1-7.97(m, 3 H), 5.31 (t, J = 6.8 Hz, 2 H), 4.11 (t, J = 6.8 Hz, 2 H); TOF-MS[M + H]⁺ 462.0 296

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(3,4-dimethoxyphenyl)ethyl]-9 H-purin-6- amine. ¹H NMR (CD₀₃OD) δ8.27 (s, 1 H), 7.22 (s, 1 H), 6.97 (s, 1 H), 6.78 (d, J = 8.0 Hz, 1 H),6.62 (d, J = 2.0 Hz, 1 H), 6.57 (dd, J = 8.0, 2.0 Hz, 1 H), 6.06 (s, 2H), 4.53 (t, J = 6.8 Hz, 2 H), 3.76 (s, 3 H), 3.71 (s, 3 H), 3.12 (t, #J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 530.0 297

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(3,4-dimethoxyphenyl)ethyl]-3H-purin-6- amine. ¹H NMR (CD₃OD) δ 8.16(s, 1 H), 7.4 (d, J = 4.0 Hz, 2 H), 6.84 (d, J = 8.4 Hz, 1 H), 6.71 (d,J = 2.0 Hz, 1 H), 6.62 (dd, J = 8.4, 2.0 Hz, 1 H), 6.19 (s, 2 H), 4.62(t, J = 6.8 Hz, 2 H), 3.81 (s, 3 H), 3.78 (s, 3 H), 3.18 (t, # J = 6.8Hz, 2 H); TOF-MS [M + H]⁺ 530.0 298

2-{6-Amino-8-[(3-methoxyphenyl)thio]-9 H- purin-9-yl}-1-phenylethanone.¹H NMR (CD₃OD) δ 8.24 (s, 1 H), 8.05 (dd, J = 8.4, 1.2 Hz, 2 H), 7.72(t, J = 7.2 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 2 H), 7.23 (t, J = 8.0 Hz, 1H), 7.06-7.02 (m, 2 H), 6.91-6.86 (m, 1 H), 5.89 (s, 2 H), 3.70 (s, 3H); TOF-MS [M + H]⁺ 392.1 299

2-{6-Amino-8-[(3-methoxyphenyl)thio]-3 H- purin-3-yl}-1-phenylethanone.¹H NMR (CD₃OD) δ 8.45 (s, 1 H), 8.13-8.09 (m, 2 H), 7.75 (dt, J = 8.0,1.2 Hz, 1 H), 7.61 (t, J = 7.6 Hz, 2 H), 7.43 (dt, J = 8.4, 1.6 Hz, 1H), 7.28- 7.24 (m, 2 H), 7.14-7.1 (m, 1 H), 6.03 (s, 2 H), 3.80 (s, 3H); TOF-MS [M + H]⁺ 392.1 300

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)phenol. ¹H NMR (CD₃OD) δ 8.27 (s, 1 H), 7.24 (s, 1 H), 7.05 (d,J = 7.6 Hz, 2 H), 7.00-6.95 (m, 3 H), 6.07 (s, 2 H), 4.52 (t, J = 6.8Hz, 2 H), 3.14 (t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 486.0 301

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)phenol. ¹H NMR (CD₃OD) δ 8.09 (s, 1 H), 7.37 (s, 1 H), 7.36 (s,1 H), 7.07 (d, J = 8.0 Hz, 2 H), 6.96 (d, J = 8.0 Hz, 2 H), 6.15 (s, 2H), 4.57 (t, J = 6.8 Hz, 2 H), 3.16 (t, J = 6.8 Hz, 2 H); TOF-MS [M +H]⁺ 486.0 302

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9- [2-(2-naphthyl)ethyl]-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.17 (s, 1 H), 7.8-7.77 (m, 1 H), 7.74(d, J = 8.4 Hz, 1 H), 7.71-7.67 (m, 1 H), 7.46 (s, 1 H), 7.45-7.40 (m, 2H), 7.25 (dd, J = 8.8, 2.0 Hz, 1 H), 7.12 (s, 1 H), 6.67 (s, 1 H), 5.99(s, 2 H), 4.58 (t, J = 6.8 Hz, 2 H), # 3.34-3.28 (m, 2 H); TOF-MS [M +H]⁺ 520.0 303

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3- [2-(2-naphthyl)ethyl]-3H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.17 (s, 1 H), 7.85-7.75 (m, 2 H),7.73-7.67 (m, 1 H), 7.51 (s, 1 H), 7.70- 7.44 (m, 2 H), 7.39 (s, 1 H),7.35 (s, 1 H), 7.29 (dd, J = 8.4, 1.6 Hz, 1 H), 6.15 (s, 2 H), 4.70 (t,J = 6.8 Hz, 2 H), 3.39 (t, J = 6.8 Hz, 2 H); # TOF-MS [M + H]⁺ 520.0 304

3-{[6-Amino-9-(2-phenylethyl)-9 H-purin-8-yl]thio}-4-methoxybenzonitrile. ¹H NMR (CD₃OD) δ 8.22 (s, 1 H), 7.77(dd, J = 10.8, 2.4 Hz, 1 H), 7.61 (d, J = 2.0 Hz, 1 H), 7.27-7.20 (m, 4H), 7.07-7.14 (m, 2 H), 4.57 (t, J = 6.8 Hz, 2 H), 3.91 (s, 3 H), 3.18(t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 403.1 305

3-{[6-Amino-3-(2-phenylethyl)-3 H-purin-8-yl]thio}-4-methoxybenzonitrile. ¹H NMR (CD₃OD) δ 9.38 (d, J = 2.0 Hz, 1H), 9.27 (s, 1 H), 9.22 (dd, J = 8.8, 2.4 Hz, 1 H), 8.65-8.57 (m, 4 H),8.46-8.39 (m, 2 H), 5.81 (t, J = 6.8 Hz, 2 H), 5.25 (s, 3 H), 4.48 (t, J= 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 403.1 306

3-({6-Amino-9-[2-(2-chlorophenyl)ethyl]- 9H-purin- 8-yl}thio)-4-methoxybenzonitrile. ¹H NMR (CD₃OD) δ 8.25 (s, 1 H), 7.65 (dd,J = 8.4, 2.0 Hz, 1 H), 7.32 (d, J = 2.0 Hz, 1 H), 7.29 (dd, J = 8.0, 1.2Hz, 1 H), 7.15 (dt, J = 7.6, 2.0 Hz, 1 H), 7.13-7.07 (m, 2 H), 6.93 (dd,J = 7.6, 2.0 Hz, 1 H), 4.53 (t, J = 6.8 Hz, # 2 H), 3.91 (s, 3 H), 3.27(t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 437.1 307

3-({6-Amino-3-[2-(2-chlorophenyl)ethyl]- 3H-purin-8-yl}thio)-4-methoxybenzonitrile. ¹H NMR (CD₃OD) δ 8.14 (s, 1H), 8.08 (d, J = 2.0 Hz, 1 H), 7.95 (dd, J = 8.8, 2.0 Hz, 1 H),7.37-7.33 (m, 2 H), 7.22 (dq, J = 7.6, 2.0 Hz, 2 H), 7.15-7.12 (m, 1 H),4.61 (t, J = 6.8 Hz, 2 H), 3.94 (s, 3 H), 3.35 (t, J = 6.8 Hz, 2 H); #TOF-MS [M + H]⁺ 437.1 308

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9- [2-(3-methoxyphenyl)ethyl]-9H-purin-6- amine. ¹H NMR (CD₃OD) δ 8.25 (s, 1 H), 7.22 (s, 1 H), 7.12(t, J = 7.6 Hz, 1 H), 7.00 (s, 1 H), 6.74 (ddd, J = 8.4, 2.8, 1.2 Hz, 1H), 6.67-6.6 (m, 2 H), 6.06 (s, 2 H), 4.53 (t, J = 6.8 Hz, 2 H), 3.70(s, 3 H), 3.14 (t, J = 6.8 Hz, # 2 H); TOF-MS [M + H]⁺ 500.0 309

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3- [2-(3-methoxyphenyl)ethyl]-3H-purin-6- amine. ¹H NMR (CD₃OD) δ 7.97 (s, 1 H), 7.29 (s, 1 H), 7.24(s, 1 H), 7.15 (t, J = 7.6 Hz, 1 H), 6.79-6.75 (m, 1 H), 6.66-6.61 (m, 2H), 6.10 (s, 2 H), 4.56 (t, J = 6.8 Hz, 2 H), 3.70 (s, 3 H), 3.17 (t, J= 6.8 Hz, 2 H); LC-MS [M + H]⁺ 500.3 310

8-[(2-Iodo-5-methoxyphenyl)thio]-9-[2-(4- iodophenyl)ethyl]-9H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.37 (s, 1 H), 8.16 (s, 1 H),7.25-7.18 (m, 3 H), 7.13-7.09 (m, 2 H), 6.69 (s, 1 H), 4.48 (t, J = 6.8Hz, 2 H), 3.48 (s, 3 H), 3.12 (t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺629.9 311

8-[(2-Iodo-5-methoxyphenyl)thio]-3-[2-(4- iodophenyl)ethyl]-3H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.35 (s, 1 H), 7.57 (s, 1 H),7.34-7.25 (m, 4 H), 6.94 (dd, J = 7.6, 2.0 Hz, 2 H), 4.46 (t, J = 6.8Hz, 2 H), 3.9 (s, 3 H), 3.18 (t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 629.9312

8-[(5-Fluoro-2-methoxyphenyl)thio]-9-(2- phenylethyl)-9 H-purin-6-amine.¹H NMR (CDCl₃) δ 8.50-8.40 (broad s, 1 H), 7.29-7.19 (m, 3 H), 7.15-7.11(m, 2 H), 7.02- 6.95 (m, 1 H), 6.91 (dd, J = 8.0, 2.8 Hz, 1 H), 6.84(dd, J = 9.2, 4.4 Hz, 1 H), 4.49 (t, J = 6.8 Hz, 2 H), 3.81 (s, 3 H),3.10 (t, J = 6.8 Hz, 2 H); LC-MS # [M + H]⁺ 396.3 313

8-[(5-Fluoro-2-methoxyphenyl)thio]-3-(2- phenylethyl)-3 H-purin-6-amine.¹H NMR (CDCl₃) δ 7.55-7.52 (m, 1 H), 7.41 (dd, J = 7.6, 2.8 Hz, 1 H),7.33-7.26 (m, 3 H), 7.23-7.16 (m, 1 H), 6.99-6.93 (m, 3 H), 4.50 (t, J =6.8 Hz, 2 H), 3.83 (s, 3 H), 3.19 (t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺396.4 314

8-[(2-Methoxy-5-methylphenyl)thio]-9-(2- phenylethyl)-9 H-purin-6-amineLC-MS [M + H]⁺ 392.4 315

8-[(2-Methoxy-5-methylphenyl)thio]-3-(2- phenylethyl)-3 H-purin-6-amine.¹H NMR (CDCl₃) δ 7.51-7.43 (m, 2 H), 7.33- 7.25 (m, 4 H), 6.98-6.94 (m,2 H), 6.91 (d, J = 8.4 Hz, 1 H), 4.49 (t, J = 6.8 Hz, 2 H), 3.81 (s, 3H), 3.19 (t, J = 6.8 Hz, 2 H), 2.35 (s, 3 H); LC-MS [M + H]⁺ 392.4 316

9-[2-(2-Chlorophenyl)ethyl]-8-[(5 -fluoro-2- methoxyphenyl)thio]-9H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.21 (s, 1 H), 7.33 (dd, J = 7.6, 1.2Hz, 1 H), 7.18 (dt, J = 7.6, 1.6 Hz, 1 H), 7.1 (dt, J = 7.6, 1.6 Hz, 1H), 7.07-6.94 (m, 3 H), 6.86 (dd, J = 9.2, 4.4 Hz, 1 H), 4.57 (t, J =7.2 Hz, 2 H), 3.79 (s, 3 H), 3.28 (t, # J = 7.2 Hz, 2 H); LC-MS [M + H]⁺430.3 317

3-[2-(2-Chlorophenyl)ethyl]-8-[(5-fluoro-2- methoxyphenyl)thio]-3H-purin-6-amine. ¹H NMR (CDCl₃) δ 7.61-7.57 (broad s, 1 H), 7.43-7.37(m, 2 H), 7.25-7.12 (m, 3 H), 6.95 (dd, J = 8.8, 4.0 Hz, 1 H), 6.84 (dd,J = 7.6, 1.6 Hz, 1 H), 4.56 (t, J = 6.8 Hz, 2 H), 3.83 (s, 3 H), 3.34(t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺ 430.3 318

9-[2-(2-Chlorophenyl)ethyl]-8-[(2-methoxy- 5-nitrophenyl)thio]-9H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.28 (s, 1 H), 8.22 (dd, J = 9.2, 2.8Hz, 1 H), 8.15 (d, J = 2.4 Hz, 1 H), 7.31 (dd, J = 7.6, 1.6 Hz, 1 H),7.15 (dt, J = 7.6, 1.6 Hz, 1 H), 7.09 (dt, J = 7.6, 1.2 Hz, 1 H), 6.98(d, J = 9.2 Hz, 1 H), 6.94 (dd, # J = 7.2, 1.6 Hz, 1 H), 4.59 (t, J =6.8 Hz, 2 H), 3.94 (s, 3 H), 3.31 (t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺457.3 319

3-[2-(2-Chlorophenyl)ethyl]-8-[(2-methoxy- 5-nitrophenyl)thio]-3H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.59 (s, 1 H), 8.23-8.21 (m, 1 H),7.52 (s, 1 H), 7.38 (dd, J = 8.0, 1.2 Hz, 1 H), 7.22 (dt, J = 7.6, 1.6Hz, 1 H), 7.11 (dt, J = 7.6, 1.2 Hz, 1 H), 7.01 (d, J = 8.8 Hz, 1 H),6.85 (dd, J = 7.6, 1.6 Hz, 1 H), 4.61 (t, # J = 6.8 Hz, 2 H), 4.01 (s, 3H), 3.41 (t, J = 6.8 Hz, 2 H); LC-MS [M + H]⁺ 457.3 320

6-{[6-Amino-9-(2-phenylethyl)-9 H-purin-8-yl]thio}-1,3-benzodioxole-5-carbonitrile. ¹H NMR (CD₃OD) δ 8.23 (s, 1H), 7.32 (s, 1 H), 7.28-7.20 (m, 3 H), 7.13-7.08 (m, 3 H), 6.17 (s, 2H), 4.56 (t, J = 6.8 Hz, 2 H), 3.19 (t, J = 6.8 Hz, 2 H); TOF-MS [M +H]⁺ 417.1 321

6-{[6-Amino-3-(2-phenylethyl)-3 H-purin-8-yl]thio}-1,3-benzodioxole-5-carbonitrile. ¹H NMR (CD₃OD) δ 8.08 (s, 1H), 7.44 (s, 1 H), 7.41 (s, 1 H), 7.30-7.20 (m, 3 H), 7.10-7.06 (m, 2H), 6.24 (s, 2 H), 4.57 (t, J = 6.8 Hz, 2 H), 3.20 (t, J = 6.8 Hz, 2 H);TOF-MS [M + H]⁺ 417.1 322

8-[(2-Iodo-5-methoxyphenyl)thio]-9-(2- phenylethyl)-9 H-purin-6-amine.¹H NMR (CDCl₃) δ 8.18 (s, 1 H), 7.78 (d, J = 8.4 Hz, 1 H), 7.32-7.24 (m,3 H), 7.40-7.10 (m, 2 H), 6.98 (d, J = 2.8 Hz, 1 H), 6.68 (dd, J = 8.4,2.8 Hz, 1 H), 4.5 (t, J = 6.8 Hz, 2 H), 3.75 (s, 3 H), 3.12 (t, J = 6.8Hz, 2 H); LC-MS [M + H]⁺ 504.3 323

8-[(2-Iodo-5-methoxyphenyl)thio]-3-(2- phenylethyl)-3 H-purin-6-amine.¹H NMR (CDCl₃) δ 7.85 (d, J = 8.4 Hz, 1 H), 7.52 (s, 1 H), 7.42 (d, J =4.4 Hz, 1 H), 7.30- 7.25 (m, 3 H), 6.98-6.94 (m, 2 H), 6.76 (dd, J =8.8, 3.2 Hz, 1 H), 4.47 (t, J = 6.8 Hz, 2 H), 3.82 (s, 3 H), 3.19 (t, J= 6.8 Hz, 2 H); LC-MS [M + H]⁺ 504.3 324

9-[2-(2-Chlorophenyl)ethyl]-8-[(2-methoxy- 5-methylphenyl)thio]-9H-purin-6-amine. LC- MS [M + H]⁺ 426.3 325

3-[2-(2-Chlorophenyl)ethyl]-8-[(2-methoxy- 5-methylphenyl)thio]-3H-purin-6-amine. ¹H NMR (CDCl₃) δ 7.54 (s, 1 H), 7.48-7.46 (m, 1 H),7.39 (dd, J = 8.0, 1.2 Hz, 1 H), 7.32-7.28 (m, 1 H), 7.25-7.21 (m, 1 H),7.15 (dt, J = 7.6, 1.2 Hz, 1 H), 6.91 (d, J = 8.4 Hz, 1 H), 6.82 (dd, J= 7.6, 1.6 Hz, 1 H), 4.55 (t, J = 6.8 Hz, # 2 H), 3.81 (s, 3 H), 3.34(t, J = 6.8 Hz, 2 H), 2.33 (s, 3 H); LC-MS [M + H]⁺ 426.3 326

6-({6-Amino-9-[2-(2-chlorophenyl)ethyl]- 9H-purin-8-yl}thio)-1,3-benzodioxole-5- carbonitrile. ¹H NMR (CD₃OD) δ8.26 (s, 1 H),7.36 (dd, J = 8.0, 1.6 Hz, 1 H), 7.33 (s, 1 H), 7.23 (dt,J = 7.6, 2.0 Hz, 1 H), 7.18-7.14 (m, 2 H), 7.09 (dd, J = 7.6, 1.6 Hz, 1H), 6.18 (s, 2 H), 4.65 (t, J = 6.8 Hz, 2 H), 3.37 (t, # J = 6.8 Hz, 2H); TOF-MS [M + H]⁺ 451.0 327

6-({6-Amino-3-[2-(2-chlorophenyl)ethyl]- 3H-purin-8-yl}thio)-1,3-benzodioxole-5- carbonitrile. ¹H NMR (CD₃OD) δ8.16 (s, 1 H), 7.43 (s, 1 H), 7.39 (s, 1 H), 7.34 (dd, J = 7.6, 1.2 Hz,1 H), 7.23 (dt, J = 7.2, 1.6 Hz, 1 H), 7.17 (dt, J = 7.6, 1.6 Hz, 1 H),7.01 (dd, J = 7.6, 1.6 Hz, 1 H), 6.25 (s, 2 H), 4.61 (t, # J = 6.8 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2 H); TOF-MS [M + H]⁺ 451.0 328

8-{[2-(Cyclopentyloxy)-5- (trifluoromethoxy)phenyl]thio}-9-(2-phenylethyl)-9 H-purin-6-amine. TOF-MS [M + H]⁺ 516.1 329

9-[2-(2-Chlorophenyl)ethyl]-8-{[2- (cyclopentyloxy)-5-(trifluoromethoxy)phenyl]thio}-9 H-purin-6- amine. TOF-MS [M + H]⁺ 550.1330

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-9H- purin-6-amine. ¹H NMR (CD₃OD) δ8.75 (s, 1 H), 8.19 (s, 1 H), 7.23 (s, 1 H), 6.97 (s, 1 H), 6.07 (s, 2H), 4.50 (t, J = 6.8 Hz, 2 H), 3.41 (t, J = 6.8 Hz, 2 H), 2.13 (s, 3 H);LC-MS [M + H]⁺ 491.1 331

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-3 H- purin-6-amine. ¹H NMR (CD₃OD)δ 8.80 (s, 1 H), 8.35 (s, 1 H), 7.40 (s, 1 H), 7.39 (s, 1 H), 6.17 (s, 2H), 4.58 (t, J = 6.8 Hz, 2 H), 3.47 (t, J = 6.8 Hz, 2 H), 2.18 (s, 3 H);LC-MS [M + H]⁺ 491.3 332

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3- {2-[(1-methyl-1-pyridin-2-ylethyl)amino]ethyl}-3 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.45 (ddd, J =4.8, 2.0, 0.8 Hz, 1 H), 8.28 (s, 1 H), 7.90 (td, J = 8.4, 2.0 Hz, 1 H),7.57 (dt, J = 8.4, 0.8 Hz, 1 H), 7.38 (ddd, J = 8.4, 4.8, 0.8 Hz, 1 H),7.23 (s, 1 H), 7.05 (s, 1 H), # 6.06 (s, 2 H), 4.68 (t, J =6.8 Hz, 2 H),3.33 (t, J = 6.8 Hz, 2 H), 1.75 (s, 6 H); TOF-MS [M + H]⁺ 528.08 333

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3- {2-[(1-methyl-1-pyridin-2-ylethyl)amino]ethyl}-3 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.42-8.39 (m, 2H), 7.91 (td, J = 7.6, 2.0 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H), 7.39(ddd, J = 6.0, 5.2, 1.2 Hz, 1 H), 7.31 (s, 1 H), 7.21 (s, 1 H), 6.12 (s,2 H), 4.71 # (t, J = 6.4 Hz, 2 H), 3.52 (t, J = 6.4 Hz, 2 H), 1.73 (s, 6H); TOF-MS [M + H]⁺ 528.08 334

8-[(2,5-Dimethoxyphenyl)thio]-9-{2-[(1-methyl-1-pyridin-2-ylethyl)amino]ethyl}- 9 H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.43 (ddd, J = 4.8, 1.6, 0.8 Hz, 1 H), 8.28 (s, 1 H), 7.89(td, J = 8.0, 2.0 Hz, 1 H), 7.57 (td, J = 8.0, 1.2 Hz, 1 H), 7.36 (ddd,J = 8.0, 4.8, 1.2 Hz, 1 H), 6.99 # (dd, J = 9.2, 0.8 Hz, 1 H), 6.96 (d,J = 9.2 Hz, 1 H), 6.92 (dd, J = 2.8, 0.8 Hz, 1 H), 4.70 (t, J = 6.4 Hz,2 H), 3.72 (s, 3 H), 3.66 (s, 3 H), 3.32 (t, J = 6.4 Hz, 2 H), 1.74 (s,6 H); TOF-MS [M + H]⁺ 466.2 335

8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(1 H- imidazol-1-yl)ethyl]-9H-purin-6-amine. ¹H NMR (CD₃CN) δ 8.33 (t, J = 1.2 Hz, 1 H), 8.18 (s, 1H), 7.28 (t, J = 1.6 Hz, 1 H), 7.13 (t, J = 1.6 Hz, 1 H), 7.01 (d, J =9.2 Hz, 1 H), 6.95 (dd, J = 9.2, 2.8 Hz, 1 H), 6.83 (d, J = 3.2 Hz, 1H), 4.69 (m, 2 H), 4.61 (m, 2 H), # 3.88 (s, 3 H), 3.72 (s, 3 H); TOF-MS[M + H]⁺ 398.14 336

8-[(2,5-Dimethoxyphenyl)thio]-3-[2-(1 H- imidazol-1-yl)ethyl]-3H-purin-6-amine. ¹H NMR (CD₃CN) δ 8.26 (s, 1 H), 8.04 (s, 1 H), 7.29(brt, J = 1.6 Hz, 1 H), 7.21 (dd, J = 2.0, 0.8 Hz, 1 H), 7.10 (brt, J =1.6 Hz, 1 H), 7.07- 7.06 (m, 2 H), 4.67-4.63 (m, 2 H), 4.61-4.58 (m, 2H), 3.78 (s, 3 H), 3.77 (s, 3 H); TOF-MS # [M + H]⁺ 398.14

Intermediate 43

Synthesis of 2-(2-chloro-ethyl)-1-propyl-piperidine

To a solution of 2-(1-propyl-piperidin-2-yl)-ethanol (0.150 g, 0.875mmol) in dichloromethane (5 mL) was added thionyl chloride (1.0 mL,13.70 mmol) at room temperature and the reaction mixture was refluxedfor 3 h. The solvent and excess thionyl chloride was removed underreduced pressure. The product was dissolved in dichloromethane andevaporated to dryness. The product was used for the next step withoutfurther purifications. GC-MS m/z 189.00

Intermediate 44

Synthesis of 1-[4-(2-bromo-ethyl)-piperidin-1-yl]-ethanone

To a solution of 1-[4-(2-hydroxy-ethyl)-piperidin-1-yl]-ethanone (0.500g, 2.92 mmol) in dichloromethane (15 mL) was added carbon tetrabromide1.45 g, 4.38 mmol), triphenyl phosphine (0.728 g, 2.77 mmol) andimidazole (0.398 g, 5.84 mmol) at 0° C. The temperature of the reactionmixture was slowly raised to room temperature and stirring continued atrt for 18 h. The reaction was diluted with dichloromethane and washedwith water. The organic layer was dried (Na₂SO₄), filtered, and thesolvent was evaporated. The product was chromatographed over silica gelusing gradient of 0-10% methanol in dichloromethane. GC-MS m/z 235

Intermediate 45

Synthesis of (S)-2-(2-Methanesulfonyloxy-ethyl)-piperidine-1-carboxylicacid tert-butyl ester

To a solution of (S)-2-(2-hydroxy-ethyl)-piperidine-1-carboxylic acidtert-butyl ester (0.300 g, 1.30 mmol) in dichloromethane (5 mL) wasadded methane sulfonylchloride 0.304 mL, 3.9 mmol) and triethylamine(0.547 mL, 3.9 mmol) at rt for 1-16 h. The reaction mixture was dilutedwith dichloromethane and washed with NaHCO₃ (10%, W/V), followed bywater. The dichloromethane layer was dried (Na₂SO₄), filtered and thesolvent was evaporated to dryness. The product was sufficiently pure forthe next step and was used without any further purification. LC-MS[M+Na] 329.9

Intermediate 46

Synthesis of toluene-4-sulfonic acid2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-ethyl ester

To a solution of 2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)ethanol(0.822 g, 4.09 mmol) (J. Med. Chem. 1990, 33, 3133) in dichloromethanewas added p-toluene sulfonyl chloride (1.71 g, 9.00 mmol) and triethylamine (2.3 mL, 16.4 mmol) and DMAP (0.050 g, 0.41 mmol) at roomtemperature and stirring continued at rt for 3 h. The reaction mixturewas diluted with dichloromethane and washed with aq NaHCO₃ (10% W/V)solution, followed by saturated NaCl solution. The organic layer wasdried (Na₂SO₄), filtered and solvent was evaporated to dryness. Theproduct was flash chromatographed over silica gel using gradient of0-10% methanol in dichloromethane. ¹H NMR (CDCl₃) δ 7.77 (d, 8.4 Hz,2H), 7.34-7.30 (m, 5H), 7.26 (m, 1H), 5.36 (m, 1H), 4.09 (t, J=6.8 Hz,2H), 3.54 (s, 2H), 2.92-2.88 (m, 2H), 2.50 (t, J=5.6 Hz, 2H), 2.44 (s,3H), 2.31 (brt, J=6.8 Hz, 2H), 2.20-1.84 (m, 2H).

Intermediates 47-86 were prepared analogously to the procedure describedfor intermediates 43-46 using the appropriate starting materials and arelisted in table 4 TABLE 4 Intermediate Structure Name and Analyticaldata 47

1-[3-(2-Chloro-ethyl)- piperidn-1-yl[-ethanone, GC-MS m/z 189.0 48

1-[2-Chloro-ethyl)piperidin- 1-yl[-ethanone. GC-MS m/z 189.0 49

2-(2-Methanesulfonyloxy- ethyl)-pyrrolidine-1- carboxylic acidtert-butyl ester. LC-MS [M + H]⁺ 294.3 50

2-(2-Methanesulfonyloxy- ethyl)-piperidine-1- carboxylic acid benzylester. LC-MS [M − H]⁺ 340.8 51

2-(2-Methanesulfonyloxy- ethyl)-pyrrolidine-1- carboxylic acid benzylester. LC-MS [M + H]⁺ 328.0 51

(2R, 4S)-4-(2- Methanesulfonyloxy-ethyl)- piperidine-1,2-dicarboxylicacid 1-tert-butylester 2- ethyl ester. LC-MS [M − H]⁺ 378.0 52

3-(2-Methanesulfonyloxy- ethyl)-piperidine-1- carboxylic acid benzylester. LC-MS [M − H]⁺ 340.1 54

3-(2-Methanesulfonyloxy- ethyl)-azetidine-1- carboxylic acid tert-butylester. LC-MS [M + H]⁺ 279.9 55

(R)-3-(2- Methanesulfonyloxy-ethyl)- pyrrolidine-1-carboxylic acidtert-butyl ester. LC-MS [M + H]⁺ 294.1 56

(R)-2-(2- Methanesylfonyloxy-ethyl)- pyrrolidine-1-carboxylic acidtert-butyl ester. LC-MS [M + H]⁺ 294.6 57

(S)-3-(2- Methanesulfonyloxy-ethyl)- pyrrolidine-1-carboxylic acidtert-butyl ester. LC-MS [M + H]⁺ 294.3 58

4-(2-bromo-ethyl)-2,2,6, 6-tetramethyl-piperidine. GC-MS m/z 248.11 59

4-(2-Bromo-ethyl)- piperidine-1-carbaldehyde. GC-MS m/z 219 60

1-Benzyl-4-(2-bromo- ethyl)-piperidine. LC-MS [M + H]⁺ 282.2 61

(R)-3-(2-(Bromo- ethylpiperidine-1- carboxylic acid tert-butyl ester.GC-MS m/z 291 62

2-(2-Bromo- ethyl)morpholine-4- carboxylic acid tert-butyl ester. GC-MSm/z 293 63

3-(2-Bromo-ethyl)- piperidine-1-carboxylic acid tert-butyl ester. GC-MSm/z 291 64

2-(2-Bromo-ethyl)- piperidine-1-carboxylic acid tert-Butyl ester. GC-MSm/z 291 65

2-(2-Bromo-ethyl)- pyrrolidine-1-carboxylic acid tert-butyl ester. GC-MS m/z 277 66

4-(2-(Bromo-ethyl)- piperidine-1-carboxylic acid benzyl ester. GC-MS m/z325 67

3-(2-Bromo-ethyl)- pyrrolydine-1-carboxylic acid tert-butyl ester. GC-MS m/z 277 68

3-(2-Bromo-ethyl)-1- trifluoromethanesulfonyl- piperidine. GC-MS m/z323.0 69

4-(2-Bromo-ethyl)-1- trifluoromethanesulfonyl- piperidine. GC-MS m/z323.00 70

2-(2-Bromo-ethyl)-1- trifluoromethanesulfonyl piperidine. GC-MS m/z 216[M-C₂H₄Br] 71

Toluene-4-sulfonic acid 2- (1-tert-butylcarbamoyl- piperidin-4-yl)-ethylester. LC-MS [M + H]⁺ 383.2 72

Toluene-4-sulfonic acid 2- (1-isopropylcarbamoyl- piperidin-4-yl)-ethylester. LC-MS [M + H]⁺ 369.2 73

Toluene-4-sulfonic acid 2- (1-ethylcarbamoyl- piperidin-4-yl)-ethylester. LC-MS [M + H]⁺ 355.2 74

Toluene-4-sulfonic acid 2- (1-tert-butylcarbamoyl- piperidin-3-yl)-ethylester. LC-MS [M + H]⁺ 383.3 75

Toluene-4-sulfonic acid 2- (1-isopropylcarbamoyl- piperidin-3-yl)-ethylester. LC-MS [M + H]⁺ 369.2 76

Toluene-4-sulfonic acid 2- (1-ethylcarbamoyl- piperidin-3-yl)-ethylester. LC-MS [M + H]⁺ 355.2 77

({4-[2-(Toluene-4- sulfonyloxy)-ethyl]- piperidine-1-carbonyl}-amino)-acetic acid ethyl ester. LC-MS [M + H]⁺ 413.5 78

1-[4-(2-Bromo-ethyl)- piperazin-1-yl]-ethanone. ¹H NMR (CDCl₃) δ 3.65-3.62 (m, 2 H), 3.50-3.47 (m, 2 H), 3.43 (t, J = 7.2 Hz, 2 H), 2.81 (t, J= 7.2 Hz, 2 H), 2.53-2.51 (m, 2 H), 2.49-2.47 (m, 2 H), 2.10 (s, 3 H).79

1-[4-(2-Bromo-ethyl)- piperazin-1-yl]-2,2- dimethyl-propan-1-one. ¹H NMR(CDCl₃): 3.68-3.65 (m, 2 H), 3.43 (t, J = 7.2 Hz, 2 H), 2.80 (t, J = 7.2Hz, 2 H), 2.51-2.48 (m, 2 H), 1.28 (s, 9 H) 80

1-[3-(2-Chloro-ethyl)- piperidin-1-yl]-2.2- dimethyl-propan-1-one. LC-MS [M + H]⁺ 232 81

Methanesulfonic acid 2-[1- (3,3-dimethyl-butyryl)- piperidin-4-yl]-ethylester. LC-MS [M + H]⁺ 305 82

2-(2-Chloro-ethyl)-1- isopropyl-piperidine. GC- MS m/z 189.0 83

1-[4-(2-Chloro-ethyl)- piperidin-1-yl]-2,2- dimethyl-propan-1-one. LC MS[M + H]⁺ 232 84

4-(2-Chloro-ethyl)-1- isobutyl-piperidine. GC-MS m/z 203.0 85

1-[3[(2-Chloro-ethyl)- piperidin-1-yl]-3,3- dimethyl-butan-1-one. GC- MSm/z 245.0 86

2-(2-Chloro-ethyl)-1- isobutyl-piperidine. GC-MS m/z 203.0

Intermediates 87 and 88

Synthesis oftrans-2-Isopropyl-4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carboxylicacid tert-butyl ester andcis-2-isopropyl-4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carboxylicacid tert-butyl ester

2-isopropyl-4-methoxycarbonylmethyl-piperidine-1-carboxylic acidtert-butyl ester was prepared as a mixture of cis and trans-isomeraccording to the known literature procedure (Org. Lett. 2000, 2, 3679).Subsequent treatment of ester with NaBH₄/LiCl, followed by addition ofTsCl in the presence of NEt₃ and catalytic quantity of DMAP, providedcis-2-isopropyl-4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carboxylicacid tert-butyl ester andcis-2-isopropyl-4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carboxylicacid tert-butyl ester, which were separated by ISCO flash chromatograph.cis-2-Isopropyl-4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carboxylicacid tert-butyl ester, ¹H NMR (CDCl₃) δ 7.79 (dt, J=8.4, 2.0 Hz, 2H),7.35 (d, J=8.4 Hz, 2H), 4.04 (m, 2H), 3.78 (ddd, J=14.0, 8.0, 2.0 Hz,1H), 3.52 (q, 8.4 Hz, 1H), 2.83 (ddd, J=14.5, 10.8, 6.8 Hz, 1H), 2.46(s, 3H), 1.86-1.76 (m, 2H), 1.69-1.59 (m, 3H), 1.52 (m, 1H), 1.45 (m,9H), 1.06 (m, 1H), 1.00 (m, 1H), 0.85 (d, J=6.4 Hz, 6H).

cis-2-Isopropyl-4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carboxylicacid tert-butyl ester, ¹H NMR (CDCl₃) δ 7.79 (dt, J=8.8, 2.2 Hz, 2H),7.35 (d, J=8.8 Hz, 2H), 4.10-4.02 (m, 2H), 3.89 (m, 1H), 3.67 (m, 1H),2.68 and 2.59 (two t, J=14.4 and 13.6 Hz, 1H), 2.46 (s, 3H), 1.93 (m,1H), 1.75 (brd, J=14.0 Hz, 1H), 1.68 (m, 1H), 1.55-1.47 (m, 3H), 1.43(s, 9H), 1.07 (dt, J=12.8, 5.2 Hz, 1H), 0.97 (m, 1H)

Intermediate 89

Synthesis of toluene-4-sulfonic acid2-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-ethyl ester

2-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yl)ethanol was prepared fromcommercially available 3-tropinone according to the literature procedure(J. Med. Chem. 2001, 44, 3937). It was converted to correspondingtosylate according to the procedure described for intermediates 46 andit was used for the next without further purification.

Intermediate 90

Synthesis of4[2-(Toluene-4-sulfonyloxy)-ethylidene]-piperidine-1-carboxylic acidtert-butyl ester

The title product was prepared in three steps sequence starting fromN-Boc 4-piperidone, by standard Wittig reaction, followed by DIBALreduction to afford 4-(2-hydroxy-ethylidene)-piperidine-1-carboxylicacid tert-butyl ester. The alcohol was treated according to theprocedure described for intermediate 46 to afford the correspondingtosylate. ¹H NMR (CDCl₃) δ 7.77 (dt, J=8.4, 2.0 Hz, 2H), 7.35 (d, J=2H),5.37 (m, 1H), 4.09 (t, J=6.4 Hz, 2H), 3.97-3.78 (m, 2H), 3.42 (t, J=6.4Hz, 2H), 2.46 (s, 3H), 2.34 (brt, J=7.2 Hz, 2H), 1.98-1.92 (m, 2H), 1.47(s, 9H).

Intermediate 91

Synthesis of toluene-4-sulfonic acid2-(8-oxa-bicyclo[3.2.1]oct-3-yl)ethyl ester

8-Oxa-bicyclo[3.2.1]oct-6-en-3-one was synthesized by the known [4+3]cycloaddition of the commercially available furan and the oxyallygenerated from 1,1,3-trichloroacetone, followed by reduction with zinc(J. Org. Chem. 1999, 64, 3398 and J. Am. Chem. Soc. 2001, 123, 5590).Internal double bond of the cycloadduct was reduced using Pd/C in MeOHto give 8-oxa-bicyclo[3.2.1]octan-3-one. The resulting ketone wassubjected to Eadsworth-Horner-Emmons condition to yield theα,β-unsatured ester. Catalytic hydrogenation of the conjugated estergave rise to an inseparable mixture (˜1:1) of diasteromers with nodiastereoselectivity. The mixture of diastereomers carried forward tothe next two steps. These steps include reduction of esters withNaBH₄/LiCl followed by treatment with TsCl in the presence of NEt₃ tofurnish the oxabicyclo[3.2.1]octaneethylmethylbenzensolfonate. ¹H NMR(CDCl₃): δ 7.81-7.78 (m, 2H), 7.37-7.34 (m, 2H), 4.35-4.28 (m, 2H),4.07-4.02 (m, 2H), 2.46 (s, 3H), 2.07 (m, 1H), 1.95-1.87 (m, 2H),1.82-1.76 (m, 1H), 1.68-1.63 (m, 2H), 1.55-1.50 (m, 2H), 1.43-1.28 (m,2H), 1.10 (m, 1H).

Intermediate 92

Synthesis of toluene-4-sulfonic acid2-(1-methyl-8-oxa-bicyclo[3.2.1]oct-3-yl)-ethyl ester

The title product was synthesized according to the procedure describedfor intermediate 91 starting from 2-methyl furan. ¹H NMR (CDCl₃): δ7.81-7.78 (m, 2H), 7.37-7.35 (m, 2H), 4.37-4.29 (m, 1H), 4.07-4.02 (m,2H), 2.46 (s, 3H), 2.10-1.96 (m, 2H), 1.89-1.50 (m, 6H), 1.39 (m, 1H),1.27 (s, 1.5H), 1.26 (s, 1.5H), 1.25 (m, 1H), 1.10 (m, 1H).

Intermediate 93

2-{1-(1-Ethyl-1H-tetrazol-5-yl)piperidin-4-yl)ethyl-4-ethylbenzenesulfonate

Intermediate 93 was prepared in three sequential steps

Step 1: N-Ethyl-4-(2-hydroxyethyl)piperidine-1-carbothioamide

To a solution of 2-(piperidin-4-yl)ethanol (509 mg, 3.94 mmol) in CH₂Cl₂(13 mL) was added isothiocyanatoethane (343 μL, 3.94 mmol). Afterstirring for 10 h at rt, the mixture was concentrated in vacuo toprovide the titled compound (716 mg, 84%): ¹H NMR (CDCl₃) δ 5.38 (brs,1H), 4.59 (d, J=13.6 Hz, 1H), 3.74-3.67 (m, 3H), 3.15 (d, J=12.8 Hz,1H), 3.00 (t, J=13.2 Hz, 2H), 2.65 (t, J=12.4 Hz, 1H), 1.81-1.72 (m,3H), 1.55-1.52 (m, 3H), 1.28-1.22 (m, 4H)

Step 2: 2-{1-(1-Ethyl-1H-tetrazol-5-yl)piperidin-4-yl}ethanol

To a mixture of N-Ethyl-4-(2-hydroxyethyl)piperidine-1-carbothioamide(200 mg, 0.93 mmol), HgCl₂ (277 mg, 1.02 mmol), and NaN₃ (181 mg, 2.78mmol) in DMF (2.5 mL) was added NEt₃ (388 μL, 2.78 mmol) at rt. Afterstirring for 10 h, the reaction mixture was filtered, and the filtercake was washed with CH₂Cl₂. The combined filtrates and washings werewashed with brine, dried (Na₂SO₄), filtered and concentrated in vacuo,and the residue was purified by SiO₂ chromatograph (60% EtOAc/hexane) toafford the titled compound (85 mg, 41%): ¹H NMR (CDCl₃) δ 4.18 (q, J=7.2Hz, 2H), 3.75 (td, J=6.8, 5.2 Hz, 2H), 3.51 (brd, J=12.4, 2H), 3.03 (td,J=12.4, 2.8 Hz, 2H), 1.84 (brd, J=14.4 Hz, 2H), 1.71 (m, 1H), 1.59 (q,J=6.8 Hz, 2H), 1.56 (t, J=7.2 Hz, 3H), 1.48-1.38 (m, 2H)

Step 3:2-{1-(1-Ethyl-1H-tetrazol-5-yl)piperidin-4-yl)ethyl-4-ethylbenzenesulfonate

The titled compound (79 mg, 55%) was obtained from2-{1-(1-ethyl-1H-tetrazol-5-yl)piperidin-4-yl}ethanol (85 mg, 0.38 mmol)according to the procedure described for intermediate 46. ¹H NMR (CDCl₃)δ 7.80 (brd, J=8.0 Hz, 2H), 7.37 (brd, J=8.0 Hz, 2H), 4.15 (q, J=7.6 Hz,2H), 4.10 (t, J=6.0 Hz, 2H), 3.46 (brd, J=12.4, 2H), 2.97 (td, J=12.4,2.0 Hz, 2H), 2.46 (s, 3H), 1.71 (brd, J=12.8 Hz, 2H), 1.67-1.63 (m, 3H),1.54 (t, J=7.6 Hz, 3H), 1.41-1.31 (m, 2H)

The following compounds are prepared according to the proceduredescribed for intermediate 46 using appropriate starting materials andsummarized in table 5. TABLE 5 Intermediate No. Structure Name andanalytical Data 94

2-{1-(1-methyl-1 H-tetrazol-5- yl)piperidine-4-yl}ethyl-4-methylbenzenesulfonate. LC-MS [M + Na]⁺ 365.5 95

2-{1-(1-isopropyl-1 H-tetrazol-5- yl)piperidine-4-yl}ethyl-4-methylbenzenesulfonate. ¹H NMR (CDCl₃) δ 7.80 (brd, J = 7.2 Hz, 2 H),(brd, J = 7.2 Hz, 2 H), 4.41 (sep, J = 6.4 Hz, 1 H), 4.10 (t, J = 5.2Hz, 2 H), 3.36 (d, J = 12.0 Hz, 2 H), 2.96 (t, J = 12.8 Hz, 2 H), 2.46(s, 3 H), # 1.72-1.60 (m, 5 H), 1.56 (d, J = 6.4 Hz, 6 H), 1.42-1.33 (m,2 H) 96

2-{1-(1 -tert-butyl-1 H-tetrazol-5- yl)piperidine-4-yl}ethyl-4-methylbenzenesulfonate. ¹H NMR (CDCl₃) δ 7.81 (d, J = 7.2 Hz, 2 H), 7.37(d, J = 7.2 Hz, 2 H), 4.41 (brt, J = 5.0 Hz, 2 H), 3.00-2.93 (m, 4 H),2.47 (s, 3 H), 1.71 (s, 9 H), 1.66-1.58 (m, 5 H), 1.39-1.29 (m, 2 H)

Intermediate 97

2-{1-(tert-Butoxycarbonyl)-3,3-dimethylpiperidine-4-yl}ethyl-4-ethyhylbenzenesulfonate

The title compound was prepared in four sequential steps.

Step 1: (E)-tert-Butyl4-{(ethoxycarbonyl)methylene}-3,3-dimethylpiperidine-1-carboxylate

To a suspension of NaH (0.212 g, 5.29 mmol) in THF (2 mL) was added asolution of triethyl 2-phosphonopropionate (1.05 mL, 5.29 mmol) in THF(2 mL) at 0° C. After the mixture was stirred for 1 h at rt, a solutionof tert-butyl-3,3-dimethyl-4-oxopiperidine-1-carboxylate (J. Org. Chem.,2001, 66, 2487) (0.600 g, 2.64 mmol) in THF was then added and stirredfor 10 h. The resulting mixture was quenched with water and the productportion was extracted with Et₂O. The combined extracts were washed withbrine, dried (Na₂SO₄), filtered and concentrated in vacuo. The residuewas purified by SiO₂ chromatography (gradient: 5% EtOAc/hexane to 40%EtOAc/hexane) to afford the titled compound (784 mg, ˜100%); ¹H NMR(CDCl₃) δ 5.73 (s, 1H), 4.15 (q, J=6.8 Hz, 2H), 3.52-3.42 (m, 2H),3.25-3.18 (m, 2H), 3.05 (t, J=5.6 Hz, 2H), 1.47 (s, 9H), 1.29 (t, J=6.8Hz, 3H), 1.12 (s, 6H)

Step 2: tert-Butyl4-{(ethoxycarbonyl)methyl}-3,3-dimethylpiperidine-1-carboxylate

A solution of (E)-tert-butyl4-{(ethoxycarbonyl)methylene}-3,3-dimethylpiperidine-1-carboxylate (784mg, 2.64 mmol) in MeOH (10 mL) containing Pd/C (131 mg) was hydrogenatedat 1 atm. After 10 h, the mixture was filtered, and the filter cake waswashed with MeOH. The combined filtrates were concentrated to afford thetitled compound (540 mg, 68%): ¹H NMR (CDCl₃) δ 4.13 (q, J=6.8 Hz, 2H),4.05 (m, 1H), 3.57 (m, 1H), 2.57 (m, 1H), 2.46 (dd, J=15.2, 3.2 Hz, 1H),1.93 (dd, J=15.2, 10.4 Hz, 1H), 1.76 (m, 1H), 1.59-1.50 (m, 2H), 1.45(s, 9H) 1.34 (m, 1H), 1.26 (t, J=6.8 Hz, 3H), 0.91 (s, 3H), 0.79 (s,3H).

Step 3: tert-Butyl4-(2-hydroxyethyl)-3,3-dimethylpiperidine-1-carboxylate

To a slurry of NaBH₄ (204 mg, 5.40 mmol) and LiCl (229 mg, 5.40 mmol) inEtOH (8 mL) was added a solution of tert-butyl4-{(ethoxycarbonyl)methyl}-3,3-dimethylpiperidine-1-carboxylate (538 mg,1.80 mmol) in THF (10 mL) at 0° C. After stirring for 10 h at rt, theresulting mixture was quenched with water and the product portion wasextracted with Et₂O. The combined extracts were dried (Na₂SO₄),filtered, and concentrated in vacuo. The residue was purified by SiO₂chromatography (gradient: 40% EtOAc/hexane to 90% EtOAc/hexane) toprovide the titled compound (275 mg, 59%).

Step 4:2-{1-(tert-Butoxycarbonyl)-3,3-dimethylpiperidine-4-yl}ethyl-4-ethyhylbenzenesulfonate

The titled compound (350 mg, 55%) was obtained from tert-butyl4-(2-hydroxyethyl)-3,3-dimethylpiperidine-1-carboxylate (275 mg, 1.07mmol) according to the procedure described for intermediate 46. ¹H NMR(CDCl₃) δ 7.79 (brd, J=8.0 Hz, 2H), 7.36 (brd, J=8.0 Hz, 2H), 4.15-3.96(m, 4H), 3.60 (m, 1H), 2.46 (s, 3H), 2.61-2.23 (m, 2H), 1.89 (m, 1H),1.44 (s, 9H), 1.26 (m, 3H), 0.84 (s, 3H), 0.74 (s, 3H)

Intermediate 98

2-(1-{(Z)-[(tert-Butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl}piperidin-4-yl)ethyl4-methyl benzenesulfonate Step 1: di-tert-Butyl{(Z)-[4-(2-hydroxyethyl)piperidin-1-yl]methylidene}biscarbamate

To a solution of 2-(piperidin-4-yl)ethanol (400 mg, 3.10 mmol) and NEt₃(864 μL, 6.20 mmol) in CH₂Cl₂ (8 mL) was added1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopsudourea (899 mg, 3.10mmol) and HgCl₂ (842 mg, 3.10 mmol). After stirring at rt for 10 h, thereaction mixture was extracted with CH₂Cl₂. The combined extracts weredried (Na₂SO₄), filtered, and concentrated in vacuo. The residue waspurified by SiO₂ chromatography (gradient: 50% EtOAc/hexane to 90%EtOAc/hexane) to provide the titled compound (969 mg, 84%): ¹H NMR(CDCl₃) δ 10.16 (brs, 1H), 4.25-4.20 (m, 2H), 3.75-3.65 (m, 2H), 2.94(t, J=12.8 Hz, 2H), 1.78-1.72 (m, 3H), 1.54 (q, J=6.4 Hz, 2H), 1.49 (s,18H), 1.38-1.29 (m, 2H).

Step 2:2-(1-{(Z)-[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl}piperidin-4-yl)ethyl4-methyl benzenesulfonate

The titled compound (446 mg, 65%) was obtained from di-tert-Butyl{(Z)-[4-(2-hydroxyethyl)piperidin-1-yl]methylidene}biscarbamate (484 mg,1.307 mmol) according to the procedure described for intermediate 46. ¹HNMR (CDCl₃) δ 10.16 (brs, 1H), 7.79 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.4Hz, 2H), 4.07 (t, J=6.0 Hz, 2H), 4.20-3.91 (m, 2H), 2.85 (t, J=12.8 Hz,2H), 2.46 (s, 3H), 1.61-1.59 (m, 5H), 1.48 (s, 9H), 1.28-1.18 (m, 2H).

Intermediate 99

2-(1-{(E)-[(tert-butoxycarbonyl)imino][(tert-butoxycarbonyl)(propyl)amino]methyl}piperidin-4-yl)ethyl4-methyl benzenesulfonate

The title compound was prepared in two sequential steps

Step 1:2-(1-{(E)-[(tert-butoxycarbonyl)imino][(tert-butoxycarbonyl)(propyl)amino]methyl}piperidin-4-yl)ethanol

To a mixture ofdi-tert-Butyl{(Z)-[4-(2-hydroxyethyl)piperidin-1-yl]methylidene}biscarbamate(200 mg, 0.538 mmol), Bu₄NI (40 mg, 0.11 mmol), and KOH (70 mg, 1.3mmol) in CH₂Cl₂ (2.5 mL) and H₂O (2.5 mL) was added iodopropane (63 μL,0.65 mmol) and refluxed for 3 h. After cooling to rt, the productportion was extracted with CH₂Cl₂, washed with brine, dried (Na₂SO₄),filtered, and concentrated in vacuo. The residue was purified by SiO₂chromatography (gradient: 40% EtOAc/hexane to 100% EtOAc) to afford thetitled compound (192 mg, 86%); LC-MS [M+H]⁺ 442.5

Step 2:2-(1-{(E)-[(tert-butoxycarbonyl)imino][(tert-butoxycarbonyl)(propyl)amino]methyl}piperidin-4-yl)ethyl4-methyl benzenesulfonate

The titled compound (189 mg, 72%) was obtained from2-(1-{(E)-[(tert-butoxycarbonyl)imino][(tert-butoxycarbonyl)(propyl)amino]methyl}piperidin-4-yl)ethanol(190 mg, 0.460 mmol) analogously to the procedure described forintermediates 46. ¹H NMR (CDCl₃) δ 7.79 (d, J=7.2 Hz, 2H), 7.36 (d,J=7.2 Hz, 2H), 4.49 (brs, 1H), 4.12-4.02 (m, 2H), 2.46 (s, 3H),1.74-1.52 (m, 7H), 1.31-1.05 (m, 2H), 0.87 (t, J=7.2 Hz, 3H)

Intermediate 100

tert-Butyl5-(2-{[4-methylphenyl)sulfonyl]oxy}ethyl)-3,4-dihydropyridine-1-(2H)-carboxylate

The title compound was prepared analogously to the procedure describedfor intermediate 46 using appropriate starting materials. ¹H NMR (CDCl₃)δ 7.79 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 6.66 and 6.56 (s, 1H),4.06 (q, J=6.8 Hz, 2H), 3.46-3.41 (m, 2H), 2.45 (s, 3H), 2.31 (t, J=7.2Hz, 2H), 1.91 (m, 1H), 1.85 (m, 1H), 1.78-1.70 (m, 2H), 1.48 (s, 9H)

Intermediate 101

1-(1-Prop-2-yn-1-yl)piperidine-4-yl)ethyl 4-methyl benzenesulfonate

The title compound was prepared according to the procedure described forintermediate 46 using appropriate starting materials. LC-MS [M+H]⁺322.1.

Intermediates 102-114 were prepared according the procedure describedfor intermediate 46 using appropriate starting materials and aresummarized in table 6. TABLE 6 Intermediate No. Structure Name andanalytical data 102

4-({4-[2-(Toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carbonyl}-amino)-butyric acid methyl ester; LC-MS [M + H]⁺413.2 103

4-({3-[2-(Toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carbonyl}-amino)-butyric acid methyl ester; LC-MS [M + H]⁺413.2 104

(S)-4-Methylsulfanyl-2-({4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1- carbonyl}-amino)-butyric acid methylester; LC-MS [M + H]⁺ 473.1 105

(S)-4-Methylsulfanyl-2-({3-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidine-1- carbonyl}-amino)-butyric acid methylester; LC-MS [M + H]⁺ 495.1 106

Toluene-4-sulfonic acid 2-(1- cyclopentanecarbonyl-piperidin-4-yl)-ethyl ester; LC-MS [M + H]⁺ 380.3 107

Toluene-4-sulfonic acid 2-(1- cyclobutanecarbonyl-piperidin-4-yl)-ethylester; LC-MS [M + H]⁺ 366.1 108

Toluene-4-sulfonic acid 2-(1- cyclopropanecarbonyl-piperidin-4-yl)-ethyl ester; LC-MS [M + H]⁺ 352.1 109

Toluene-4-sulfonic acid 2-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]- ethyl ester; LC-MS [M + H]⁺ 366.2110

Toluene-4-sulfonic acid 2-[1-(2-methyl-cyclopropanecarbonyl)-piperidin-4-yl]- ethyl ester; LC-MS [M + H]⁺ 366.2111

Toluene-4-sulfonic acid 2-[1-(2,2,3,3-tetramethyl-cyclopropanecarbonyl)- piperidin-4-yl]-ethyl ester; LC-MS[M + H]⁺ 408.4 112

Toluene-4-sulfonic acid 2-[1-((1R,2S)-2-fluoro-cyclopropanecarbonyl)-piperidin- 4-yl]-ethyl ester; LC-MS [M +H]⁺ 408.4 113

Toluene-4-sulfonic acid 2-[1-(2,2- difluoro-cyclopropanecarbonyl)-piperidin-4-yl]-ethyl ester; LC-MS [M + H]⁺ 388.1 114

Toluene-4-sulfonic acid 2-[1-(1- trifluoromethyl-cyclopropanecarbonyl)-piperidin-4-yl]-ethyl ester; LC-MS [M + H]⁺ 420.1

Examples 337 and 3382-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-piperidine-1-carboxylicacid ethyl ester and2-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-piperidine-1-carboxylicacid ethyl ester

A mixture of 8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine (0.29g, 0.66 mmol), (2-chloro-ethyl)-piperidine-1-carboxylic acid ethyl ester(0.174 g, 0.79 mmol), and Barton's base (0.163 mL, 0.79 mmol) in DMF (3mL) was heated at 90-100° C. for 15 h. The reaction mixture was thenallowed to reach ambient temperature. After removal of solvent underreduced pressure, the residue was purified by preparative HPLC [X-Terraprep-RP18 10 um, 19×250 mm (waters), Mobile phase: solvent A: Water HPLCgrade containing 0.01% TFA, and solvent B: acetonitrile containing 0.01%TFA, general eluting gradient—solvent B 15% to 80% over 15 to 25 minutesrun time]. After lyophilization of HPLC fractions N-9 and N-3 isomerswere isolated as trifluoroacetate salts.2-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-piperidine-1-carboxylicacid ethyl ester. ¹H NMR δ (CD₃OD) 8.29 (s, 1H), 7.05-6.97 (m, 3H),4.39-4.30 (m, 2H), 4.21-4.15 (m, 1H), 4.09-3.9 (m, 3H), 3.70 (d, 5.2 Hz,2H), 3.75 (s, 3H), 3.73 (s, 3H), 2.98-2.88 (m, 1H), 2.34-2.28 (m, 1H),2.02-1.98 (m, 1H), 1.78-1.70 (m, 1H), 1.66-1.58 (m, 2H), 1.34-1.24 (m,4H); LC-MS TOF [M+H]⁺ 487.2.2-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-piperidine-1-carboxylicacid ethyl ester. ¹H NMR δ (CD₃OD) 8.41 (s, 1H), 7.2 (s, 1H), 7.12 (m,2H), 4.32-4.30 (m, 2H), 4.08 (m, 1H), 3.79 (s, 3H), 3.78 (s, 3H),3.48-4.41 (m, 1H), 3.36-3.35 (m, 3H), 3.2-3.17 (m, 1H), 3.13-3.12 (m,2H), 1.7-1.6 (m, 5H), 1.28-1.22 (m, 3H); LC-MS TOF [M+H]⁺ 487.2.

Examples 339-464 were prepared analogously to the procedure describedfor examples 337 and 338 and are summarized in table 7. All compoundswere isolated as a trifluoroacetate salts. Example No. Structure Nameand analytical data 339

Ethyl 2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5- yl)thio]-9H-purin-9- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (CD₃OD) δ 8.29 (s,1 H), 7.26 (s, 1 H), 7.14 (s, 1 H), 6.08 (s, 2 H), 4.38-4.3 (m, 2 H),4.23-4.18 (m, 1 H), 4.09-4.0 (m, 3 H), 3.0-2.94 (m, 1 H), 2.36-2.26 (m,2 H), 2.11- 2.01 (m, 2 H), # 1.91-1.82 (m, 2 H), 1.7-1.6 (m, 2 H),0.99-0.96 (m, 3 H); LC-MS [M + H]⁺ 549.3. 340

Ethyl 2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5- yl)thio]-3H-purin-3- carboxylate. ¹H NMR (CD₃OD) δ 8.49 (s, 1 H), 7.36 (s, 1 H),7.35 (s, 1 H), 6.15 (s, 2 H), 4.34-4.29 (m, 3 H), 4.11-4.05 (m, 3 H),3.97-3.9 (m, 1 H), 2.9-2.8 (m, 1 H), 2.58-2.49 (m, 1 H), 2.03- 2.01 (m,1 H), 1.91-1.82 (m, 1 H), 1.79-1.7 # (m, 2 H), 1.66-1.58 (m, 2 H),0.99-0.96 (m, 3 H); LC- MS [M + H]⁺ 549.3. 341

tert-Butyl 4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5- yl)thio]-9H-purin-9- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (Acetone-d₆) δ8.28 (s, 1 H), 7.26 (s, 1 H), 6.92 (s, 1 H), 6.11 (s, 2 H), 4.34 (t, J =7.2 Hz, 2 H), 4.1-4.0 (m, 2 H), 2.07-2.05 (m, 4 H), 1.8-1.71 (m, 5 H),1.46 (s, 9 H); LC-MS # [M + H]⁺ 577.4. 342

tert-Butyl 4-(2-{6-amino-8- [(2,5-dimethoxyphenyl)thio]- 9H-purin-9-yl}ethyl)piperidine- 1-carboxylate. ¹H NMR (Acetone-d₆) δ 8.24(s, 1 H), 7.07 (d, J = 9.2 Hz, 1 H), 6.96 (dd, J = 9.2, 2.8 Hz, 1 H),6.86 (d, J = 2.8 Hz, 1 H), 4.40 (t, J = 7.6 Hz, 2 H), 4.40-3.9 (m, 2 H),3.8 (s, 3 H), 3.7 (s, 3 H), # 2.06-2.0 (m, 3 H), 1.78-1.73 (m, 4 H),1.42 (s, 9 H), 1.12-1.0 (m, 2 H); LC-MS [M + H]⁺ 515.5. 343

tert-Butyl 4-(2-{6-amino-8- [(2,5-dimethoxyphenyl)thio]- 3H-purin-3-yl}ethyl)piperidine- 1-carboxylate. ¹H NMR (Acetone-d₆) δ 8.58(s, 1 H), 7.29 (d, J = 2.8 Hz, 1 H), 7.09 (d, J = 8.8 Hz, 1 H), 7.03(dd, J = 8.8, 2.8 Hz, 1 H), 4.46 (t, J = 7.6 Hz, 2 H), 4.41-3.9 (m, 2H), 3.80 (s, 3 H), 3.78 # (s, 3 H), 1.93-1.87 (m, 2 H), 1.68-1.60 (m, 2H), 1.52-1.39 (m, 3 H), 1.42 (s, 9 H), 1.1-1.0 (m, 2 H); LC-MS [M + H]⁺515.5. 344

tert-Butyl 4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5- yl)thio]-3H-purin-3- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (Acetone- d₆) δ8.55 (s, 1 H), 7.36 (s, 1 H), 7.29 (s, 1 H), 6.18 (s, 2 H), 4.46 (t, J =7.2 Hz, 2 H), 2.22-2.20 (m, 1 H), 2.04-2.01 (m, 2 H), 1.93- 1.89 (m, 3H), 1.74-1.71 (m, 2 H), # 1.52-1.49 (m, 1 H), 1.44 (s, 9 H), 1.1-1.0 (m,2 H); LC-MS [M + H]⁺ 577.4. 345

tert-Butyl 3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5- yl)thio]-3H-purin-3- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (DMSO- d₆) δ 8.6(s, 1 H), 7.5 (s, 1 H), 7.4 (s, 1 H), 6.15 (s, 2 H), 4.4-4.3 (m, 2 H),3.8-3.4 (m, 5 H), 2.90-2.70 (m, 1 H), 2.52-2.49 (m, 2 H), 1.90-1.50 (m,3 H), 1.4 (s, 9 H); # TOF LC-MS [M + H]⁺ 577.1 346

tert-Butyl 3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5- yl)thio]-9H-purin-9- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (Acetone- d₆) δ8.43 (s, 1 H), 7.29 (s, 1 H), 7.08 (s, 1 H), 6.15 (s, 2 H), 4.42 (t, J =7.2 Hz, 2 H), 3.86-3.76 (m, 2 H), 2.91-2.85 (m, 2 H), 1.77- 1.69 (m, 2H), 1.65-1.49 (m, # 5 H), 1.48 (s, 9 H); TOF LC-MS [M + H]⁺ 577.1 347

tert-Butyl 3-(2-{6-amino-8- [(2,5-dimethoxyphenyl)thio]- 9H-purin-9-yl}ethyl)piperidine- 1-carboxylate. ¹H NMR (DMSO- d₆) δ 8.27(s, 1 H), 7.05 (d, J = 8.8 Hz, 1 H), 6.90 (dd, J = 8.8, 2.8 Hz, 1 H),6.59 (d, J = 2.8 Hz, 1 H), 4.22 (t, J = 7.2 Hz, 2 H), 3.75 (s, 3 H),3.62 (s, 3 H), 2.75-2.68 (m, # 1 H), 2.52-2.49 (m, 6 H), 1.8-1.7 (m, 1H), 1.58-1.50 (m, 2 H), 1.36 (s, 9 H), 1.1-1.0 (m, 1 H); TOF LC-MS [M +H]⁻ 515.2 348

8-[(2,5-Dimethoxyphenyl)thio]- [2-(tetrahydro-2 H-pyran-4- yl)ethyl]-9H-purin-6-amine ¹H NMR (DMSO-d₆) δ 8.24 (s, 1 H), 7.05 (d, J = 9.2 Hz, 1H), 6.88 (dd, J = 9.2, 2.8 Hz, 1 H), 6.52 (d, J = 2.8 Hz, 1 H), 4.22 (t,J = 5.6 Hz, 2 H), 3.76 (s, 3 H), 3.75-3.73 (m, 3 H), 3.61 (s, 3 H),3.16-3.10 # (m, 2 H), 1.59-1.51 (m, 4 H), 1.12-1.04 (m, 2 H); TOF LC-MS[M + H]⁺ 416.2 349

8-[(2,5-Dimethoxyphenyl)thio]-3- [2-(tetrahydro-2 H-pyran-4- yl)ethyl]-3H-purin-6-amine. TOF LC-MS [M + H]⁺ 416.2 350

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(tetrahydro-2 H-pyran-4-yl)ethyl]-3 H-purin-6-amine. TOF LC-MS [M + H]⁺ 478.1 351

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-3 H- purin-6-amine. ¹H NMR (DMSO-d₆) δ7.56-7.52 (m, 3 H), 6.11 (s, 2 H), 4.34-4.33 (m, 2 H), 1.87-1.80 (m, 5H), 1.32 (s, 6 H), 1.29 (s, 6 H), 1.14-1.12 (m, 2 H); TOF LC-MS [M + H]⁺533.1 352

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(1-methylpyrrolidin-2-yl)ethyl]-3 H-purin-6-amine. LC-MS [M + H]⁻ 475.4 353

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(tetrahydro-2 H-pyran-4-yl)ethyl]-9 H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.19 (s, 1 H), 7.39(s, 1 H), 6.83 (s, 1 H), 6.09 (s, 2 H), 4.18 (t, J = 8.0 Hz, 2 H), 3.78(d, J = 8.0, 2 H), 3.20-3.14 (m, 3 H), 1.62-1.56 (m, 4 H), 1.16-1.14 (m,2 H); # TOF LC-MS [M + H]⁺ 478.1 354

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-9 H- purin-6-amine. ¹H NMR (DMSO-d₆) δ8.19 (s, 1 H), 7.40 (s, 1 H), 6.82 (s, 1 H), 6.09 (s, 2 H), 4.20 (t, J =7.6 Hz, 2 H), 1.81-1.78 (m, 3 H), 1.62-1.60 (m, 2 H), 1.31 (s, 6 H),1.26 (s, 6 H), 1.10 (d, J = 7.6 Hz, 2 H); # TOF LC- MS [M + H]⁺ 533.1355

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-methylpyrrolidin-2-yl)ethyl]-9 H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.42 (s, 1 H), 6.60-6.50(m, 2 H), 6.10 (s, 2 H), 4.40-4.20 (m, 2 H), 3.07-2.99 (m, 2.77-1.78 (m,5 H), 2.52-2.48 (m, 5 H); LC-MS [M + H]⁺ 477.3 356

9-[2-(1-Adamantyl)ethyl]-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-6-amine. LC-MS [M + H]⁺ 528.4 357

3-[2-(1-Adamantyl)ethyl]-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-6-amine. LC-MS [M + H]⁺ 528.4 358

4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. LC-MS [M + H]⁺ 443.5 359

4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-3 H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. LC-MS [M + H]⁺ 443.5 360

8-[(2,5-Dimethoxyphenyl)thio]-3- [2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-3 H-purin-6-amine. TOF LC-MS [M + H]⁺ 471.2 361

8-[(2,5-Dimethoxyphenyl)thio]-9- [2-(2,2,6,6-tetramethylpiperidin-4-yl)ethyl]-9 H-purin-6-amine. ¹H NMR δ (DMSO-d₆) 8.19 (s, 1 H), 7.05 (d,J = 8.8 Hz, 1 H), 6.80 (dd, J = 8.8, 3.2 Hz, 1 H), 6.46 (d, J = 3.2 Hz,1 H), 4.22-4.20 (m, 2 H), 3.77 (s, 3 H), 3.62 (s, 3 H), 2.46-2.45 (m, 2H), 1.76-1.73 (m, 2 H), # 1.59-1.57 (m, 2 H), 1.29 (s, 6 H), 1.23 (s, 6H), 1.10-1.00 (m, 1 H); TOF LC-MS [M + H]⁺ 471.3 362

tert-Butyl 4-(2-{6-amino-8-[(2,5- diethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)piperidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ8.16 (s, 1 H),6.99 (d, J = 9.2 Hz, 1 H), 6.82 (dd, J = 9.2, 2.8 Hz, 1 H), 6.45 (d, J =2.8 Hz, 1 H), 4.2-4.16 (m, 4 H), 4.0-3.97 (m, 3 H), 3.87-3.84 (m, 6 H),2.52-2.49 (m, 4 H), 1.37 # (s, 9 H) 1.23-1.17 (m, 6 H); LC-MS [M + H]⁺543.2. 363

(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)piperidine-1- carbaldehyde. ¹H NMR (DMSO-d₆) δ8.21 (s, 1 H),7.94 (s, 1 H), 7.40 (s, 1 H), 6.85 (s, 1 H), 6.09 (s, 2 H), 4.34 (t, J =6.8 Hz, 2 H), 4.12-4.00 (m, 1 H), 3.70-3.60 (m, 4 H), 2.95-2.90 (m, 2H), 1.75-1.70 (m, 4 H); LC/MS # TOF [M + H]⁺ 505.1 364

9-[2-(1-Acetylpiperidin-4-yl)ethyl]- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9 H-purin-6-amine. LC-MS [M + H]⁺ 519.0 365

3-[2-(1-Acetylpiperidin-4-yl)ethyl]- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3 H-purin-6-amine. LC-MS [M + H]⁺ 519.0 366

[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[1-(methylsulfonyl)piperidin-4- yl]ethyl}-3 H-purin-6-amine. LC-MS [M + H]⁺557.0 367

tert-Butyl 2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)morpholine-4- carboxylate. ¹H NMR (Acetone-d₆) δ 8.36(s, 1 H), 7.26 (s, 1 H), 7.05 (s, 1 H), 6.14 (s, 2 H), 4.47 (t, J = 6.4Hz, 2 H), 3.85-3.80 (m, 4 H), 3.41 (t, J = 6.4 Hz, 2 H), 3.20-2.70 (m, 3H), 1.41 (s, # 9 H); TOF LC-MS [M + H]⁺ 579.1 368

tert-Butyl 2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)morpholine-4- carboxylate. ¹H NMR (Acetone-d₆) δ 8.55(s, 1 H), 7.34 (s, 1 H), 7.28 (s, 1 H), 6.17 (s, 2 H), 4.54 (t, J = 6.0Hz, 2 H), 3.79-3.76 (m, 4 H), 3.42-3.33 (m, 2 H), 3.10-2.80 (m, 3 H),1.42 (s, 9 H); TOF # LC-MS [M + H]⁺ 579.1 369

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(methylsulfonyl)piperidin-3- yl]ethyl}-9 H-purin-6-amine. ¹H NMR (CD₃OD)δ 8.20 (s, 1 H), 7.3 (s, 1 H), 7.10 (s, 1 H), 6.08 (s, 2 H), 4.33 (t, J= 6 Hz, 2 H), 3.61-3.60 (m, 2 H), 3.14-3.12 (m, 2 H), 2.80 (s, 3 H),1.90-1.89 (m, 1 H), 1.81-1.75 (m, 4 H), # 1.75-1.62 (m, 2 H); LC-MS [M +H]⁺ 555.1 370

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[1-(methylsulfonyl)piperidin-3- yl]ethyl}-3 H-purin-6-amine. ¹H NMR (CD₃OD)δ 8.53 (s, 1 H), 8.28 (s, 1 H), 7.40 (s, 1 H), 6.05 (s, 3 H), 4.47 (t, J= 6 Hz, 2 H), 3.52- 3.40 (m, 2 H), 3.14-3.12 (m, 2 H), 2.80 (s, 3 H),1.96-1.84 (m, 1 H), 1.82-1.80 (m, 4 H), # 1.70-1.54 (m, 2 H); LC-MS [M +H]⁺ 555.1 371

8-[(2,5-Dimethoxyphenyl)thio]-9- {2-[1-(methylsulfonyl)piperidin-2-yl]ethyl}-9 H-purin-6-amine. LC-MS [M + H]⁺ 493.2 372

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(methylsulfonyl)piperidin-2- yl]ethyl}-9 H-purin-6-amine. ¹H NMR (CD₃OD)δ 8.31 (s, 1 H), 7.27 (s, 1 H), 7.20 (s, 1 H), 6.09 (s, 2 H), 4.35 (t, J= 8.4 Hz, 2 H), 3.30-3.20 (m, 2 H), 3.00 (s, 3 H), 2.48-2.30 (m, 2 H),2.03-2.00 (m, 2 H), 1.70-1.62 # (m, 5 H); LC-MS [M + H]⁺ 555.1 373

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[1-(methylsulfonyl)piperidin-2- yl]ethyl}-3 H-purin-6-amine. LC-MS [M + H]⁺555.1 374

9-(2-Cycloheptylethyl)-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.23 (s, 1 H), 7.30 (d, J = 9.2 Hz, 1 H), 6.87(dd, J = 9.2, 3.2 Hz, 1 H), 6.50 (d, J = 3.2 Hz, 1 H), 4.15 (t, J = 6.8Hz, 2 H), 3.76 (s, 3 H), 3.75-3.71 (m, 2 H), 3.60 (s, 3 H), 1.63-1.42(m, 13 H); # TOF LC-MS [M + H]⁺ 427.3 375

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(undecafluorocyclohexyl)ethyl]-9 H- purin-6-amine. TOF LC-MS [M + H]⁺674.0 376

3-(2-Cycloheptylethyl)-8-[(2,5- dimethoxyphenyl)thio]-3 H-purin-6-amine. TOF LC-MS [M + H]⁺ 427.3 377

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(undecafluorocyclohexyl)ethyl]-3 H- purin-6-amine. TOF LC-MS [M + H]⁺674.0. 378

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(methylsulfonyl)piperidin-4- yl]ethyl}-9 H-purin-6-amine. ¹H NMR (CD₃OD)δ 8.20 (s, 1 H), 7.30 (s, 1 H), 7.10 (s, 1 H), 6.08 (s, 2 H), 4.32 (t, J= 7.2 Hz, 2 H), 3.70-3.69 (m, 2 H), 3.25-3.12 (m, 2 H), 2.81 (s, 3 H),1.93-1.91 (m, 2 H), 1.82-1.76 (m, 2 H), # 1.44-1.30 (m, 3 H); LC-MS [M +H]⁺ 555.3 379

8-(1,3-Benzodioxol-5-ylthio)-9-{2- [1-(methylsulfonyl)piperidin-4-yl]ethyl}-9 H-purin-6-amine. LC-MS [M + H]⁺ 555.0 380

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(1H-imidazol-1- yl)ethyl]-3H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.90 (s, 1 H), 8.39 (s, 1 H), 7.54 (brs, 2 H), 7.36 (s, 1 H), 7.30 (s, 1 H), 6.15 (s, 2 H), 4.90-4.80 (m, 4H); TOF LC-MS [M + H]⁺ 460.1 381

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1H-imidazol-1- yl)ethyl]-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.92 (t, J = 1.2 Hz, 1 H), 8.24 (s, 1H), 7.56-7.53 (m, 2 H), 7.26 (s, 1 H), 7.13 (s, 1 H), 6.09 (s, 2 H),4.80 (s, 4 H); TOF LC-MS [M + H]⁺ 460.5 382

9-[2-(4-Acetylpiperazin-1-yl)ethyl]- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.33 (s, 1 H), 7.27 (s, 1H), 7.22 (s, 1 H), 6.08 (s, 2 H), (t, J = 5.6 Hz, 2 H), 3.79-3.66 3 H),3.36 (m, 1 H), 3.17-3.11 4 H), 3.30 (br t, J = 5.6 Hz, 2 H), (s, 3 H);TOF LC-MS [M + H]⁺ 520.1 383

3-[-(4-Acetylpiperazin-1-yl)ethyl]- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio[-3 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.53 (s, 1 H), 7.38 (s, 1H), 7.37 (s, 1 H), 6.16 (s, 2 H), 4.67 (t, J = 4.8 Hz, 2 H), 3.70-3.61(m, 4 H), 3.30 (t, J = 4.8 Hz, 2 H), 3.00- 2.94 (m, 4 H), 2.12 (s, 3 H);TOF LC- # MS [M + H]⁺ 520.1 384

8-[(2,5-Dimethoxyphenyl)thio]-9- [2-(undecafluorocyclohexyl)ethyl]- 9H-purin-6-amine. ¹H NMR (Acetone-d₆) δ 8.65 (s, 1 H), 7.27 (d, J = 3.2Hz, 1 H), 7.07-7.02 (m, 2 H), 4.80 (t, J = 8.0 Hz, 2 H), 3.78 (s, 3 H),3.75 (s, 3 H), 2.15 (t, J = 8.0 Hz, 2 H); TOF LC-MS [M + H]⁺ 612.1 385

8-[(2,5-Dimethoxyphenyl)thio]-3- [2-(undecafluorocyclohexyl)ethyl]- 3H-purin-6-amine. ¹HNMR (Acetone-d₆) δ 8.38 (s, 1 H), 7.06 (d, J = 8.8Hz, 1 H), 6.95 (dd, J = 8.8, 2.8 Hz, 1 H), 6.86 (d, J = 2.8 Hz, 1 H),4.70 (t, J = 8.4 Hz, 2 H), 3.80 (s, 3 H), 3.71 (s, 3 H), 2.94 (d, J =8.4 Hz, 2 H); # TOF LC-MS [M + H]⁺ 612.1 386

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-propylpiperidin-2-yl)ethyl]-9 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.34 (s, 1 H), 7.30 (s, 1H), 7.22 (s, 1 H), 6.10 (s, 2 H), 4.46-4.14 (m, 2 H), 2.57-2.50 (m, 2H), 2.35-2.26 (m, 3 H), 2.20-2.14 (m, 2 H), 2.01-1.84 (m, 3 H), 1.80-1.60 (m, 5 H), 1.01 (t, J = 7.7 Hz, # 3 H); LC-MS [M + H]⁺ 519.0 387

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(trifluoromethyl)sulfonyl]piperidin 4-yl}ethyl)-9 H-purin-6-amine. LC-MS [M + H]⁺ 609.3 388

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-{1-[(trifluoromethyl)sulfonyl]piperidin 4-yl}ethyl)-3 H-purin-6-amine. LC-MS [M + H]⁺ 609.0 389

tert-Butyl 4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3- yl}ethylidene)piperidine-1- carboxylate. ¹H NMR (CD₃OD) δ8.45 (s, 1 H), 7.38 (s, 1 H), 7.37 (s, 1 H), 6.16 (s, 2 H), 5.23 (s, 1H), 4.48 (t, J = 6.8 Hz, 2 H), 3.69 (brs, 2 H), 3.49-3.44 (m, 2 H), 2.62# (t, J = 6.8 Hz, 2 H), 2.18- 2.13 (m, 2 H), 1.46 (s, 9 H); LC-MS [M +H]⁺ 575.5 390

tert-Butyl 4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9- yl}ethylidene)piperidine-1- carboxylate. ¹H NMR (CD₃OD) δ8.18(s, 1 H), 7.24 (s, 1 H), 7.01 (s, 1 H), 6.07 (s, 2 H), 5.17 (s, 1 H),4.36 (t, J = 6.4 Hz, 2 H), 3.69 (s, 2 H), 3.52-3.44 (m, 2 H), 2.53 (t, J= 6.4 Hz, 2 H), 2.24-2.18 (m, 2 H), 1.44 (s, # 9 H); LC-MS [M + H]⁺575.0 391

tert-Butyl (3S)-3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidine-1- carboxylate. LC-MS [M + H]⁺ 577.3 392

tert-Butyl (3R)-3-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5- yl)thio]-9H-purin-9- yl}ethyl)piperidine-1-carboxylate. ¹H NMR (Acetone-d₆) δ 8.32(s, 1 H), 7.26 (s, 1 H), 6.98 (s, 1 H), 6.12 (s, 2 H), 4.36 (t, J = 7.2Hz, 2 H), 3.85-3.80 (m, 2 H), 2.86 (t, J = 6.4 Hz, 2 H), 2.00-1.60 (m, 4H), 1.50- # 1.20 (m, 3 H), 1.41 (s, 9 H); TOF LC-MS [M + H]⁺ 577.3 393

tert-Butyl (3R)-3-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5- yl)thio]-3H-purin-3- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (Acetone-d₆) δ8.61 (s, 1 H), 7.36 (s, 1 H), 7.30 (s, 1 H), 6.17 (s, 2 H), 4.48 (t, J =6.4 Hz, 2 H), 3.83-3.76 (m, 3 H), 3.62-3.59 (m, 1 H), 2.90-2.79 (m, 3H), 1.91- 1.84 (m, 4 H), 1.45 (s, 9 H); TOF # LC-MS [M + H]⁺ 577.3 394

tert-Butyl (2R)-2-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5- yl)thio]-9H-purin-9- yl}ethyl)piperidine-1-carboxylate. ¹H NMR (Acetone-d₆) δ 8.30(s, 1 H), 7.25 (s, 1 H), 6.87 (s, 1 H), 6.10 (s, 2 H), 4.40-4.00 (m, 2H), 3.70- 3.60 (m, 2 H), 2.10-1.80 (m, 5 H), 1.70-1.50 (m, 6 H),1.90-1.50 (m, 9 H), 1.40 (s, 9 H); TOF LC-MS # [M + H]⁺ 577.4 395

tert-Butyl (2R)-2-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5- yl)thio]-3H-purin-3- yl}ethyl)piperidine-1- carboxylate. ¹H NMR (Acetone-d₆) δ8.45(s, 1 H), 7.36 (s, 1 H), 7.30 (s, 1 H), 6.19 (s, 2 H), 4.42 (d, J = 7.6Hz, 2 H), 2.75-2.6 (m, 6 H), 2.42- 2.40 (m, 2 H), 2.20-2.00 (m, 3 H),1.35 (s, 9 H); TOF LC-MS # [M + H]⁺ 579.4 396

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(trifluoromethyl)sulfonyl]piperidin 2-yl}ethyl)-9 H-purin-6-amine. LC-MS [M + H]⁺ 609.1 397

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-{1-[(trifluoromethyl)sulfonyl]piperidin 2-yl}ethyl)-3 H-purin-6-amine. LCMS [M + H]⁺ 609.1 398

tert-Butyl [cis-4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9- }ethyl)cyclohexyl]carbamate. ¹H NMR (Acetone-d₆) δ 8.3 (s, 1H), 7.25 (s, 1 H), 6.94 (s, 1 H), 6.12 (s, 2 H), 4.31 (t, J = 7.2 Hz, 2H), 1.80- 1.50 (m, 12 H), 1.39 (s, 9 H); LC-MS [M + H]⁺ 591.5 399

tert-Butyl [cis-4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3- yl}ethyl)cyclohexyl]carbamate. ¹H NMR (Acetone-d₆) δ 8.29 (s,1 H), 7.25 (s, 1 H), 6.93 (s, 1 H), 6.11 (s, 2 H), 4.31 (t, J = 7.2 Hz,2 H), 1.76- 1.50 (m, 12 H), 1.39 (s, 9 H); LC-MS [M + H]⁺ 591.5 400

9-[2-(1-Acetylpiperidin-3-yl)ethyl]- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.16 (d, J = 2.8 Hz, 1 H),7.26 (d, J = 2.0 Hz, 1 H), 7.07 (d, J = 6.8 Hz, 1 H), 6.08 (s, 2 H),4.38- 3.90 (m, 2 H), 3.47-3.36 (m, 2 H), 3.15-3.11 (m, 3 H), 2.70 (s, 3H), 2.09-2.07 (m, 2 H), 1.78-1.69 (m, # 2 H), 1.35 (s, 2 H); LC-MS [M +H]⁺ 519.0 401

3-[2-(1-Acetylpiperidin-3-yl)ethyl]- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3 H-purin-6-amine. LC-MS [M + H]⁺ 519.0 402

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(trifluoromethyl)sulfonyl]piperidin 3-yl}ethyl)-9 H-purin-6-amine. ¹HNMR δ (CD₃OD), 8.17 (s, 1 H), 7.25 (s, 1 H), 7.06 (s, 1 H), 6.07 (s, 2H), 4.33-4.29 (m, 2 H), 3.83-3.70 (m, 2 H), 3.50-3.48 (m, 2 H), 3.14-3.12 (m, 2 H), 1.99-1.93 (m, 1 H), 1.79-1.78 # (m, 2 H), 1.61-1.59 (m, 2H); LC-MS [M + H]⁺ 609.1 403

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-{1-[(trifluoromethyl)sulfonyl]piperidin- 3-yl}ethyl)-3 H-purin-6-amine. LC-MS [M + H]⁺ 609.0 404

8-[(6-Bromol,3-benzodioxal-5- yl)thio]-3-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-3- yl)ethyl]-3 H-purin-6-amine. TOFLC-MS [M + H]⁺ 514.1 405

8-[(2,5-Dimethoxyphenyl)thio]-9- [2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-3-yl)ethyl]-9 H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.20 (s, 1 H),7.05 (d, J = 9.2 Hz, 1 H), 6.80 (dd, J = 9.2, 2.8 Hz, 1 H), 6.50 (d, J =2.8 Hz, 1 H), 5.20 (s, 1 H), 4.12-4.10 (m, 2 H), 3.77 (s, 3 H), 3.60 (s,3 H), 2.32-1.98 (m, 6 H), 1.24 (s, 3 H), # 0.96-0.94 (m, 2 H), 0.86 (s,3 H); LC- MS [M + H]⁺ 452.5 406

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-5-methyl-2,4-dihydro-3 H- pyrazol-3-one. ¹H NMR (Acetone- d₆)δ 8.35 (s, 1 H), 7.36 (s, 1 H), 7.29 (s, 1 H), 6.18 (s, 2 H), 4.52-4.48(m, 2 H), 2.96-2.92 (m, 2 H), 2.03 (m, 1 H), 1.33 (s, 3 H); LC-MS [M +H]⁺ 490.2 407

4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9 H-purin-9-yl}ethyl)-5-methyl-2,4-dihydro-3 H- pyrazol-3-one. ¹H NMR (DMSO-d₆) δ8.31 (s, 1 H), 7.25 (d, J = 3.2 Hz, 1 H), 7.19 (d, J = 9.2 Hz, 1 H),7.12 (dd, J = 9.2, 3.2 Hz, 1 H), 4.40-4.30 (m, 2 H), 3.74 (s, 3 H), 3.72(s, 3 H), 2.78-2.70 (m, 2 H), 1.87 # (s, 3 H), 0.95-0.87 (m, 1 H); LC-MS[M + H]⁺ 428.2 408

4-(2-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-3 H-purin-3-yl}ethyl)-5-methyl-2,4-dihydro-3 H- pyrazol-3-one. LC-MS [M + H]⁺ 428.2409

Benzyl 4-(2-{6-amino-8-[(6-bromo- 1,3-benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)piperidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ 8.18 (s,1 H), 7.39-7.31 (m, 6 H), 6.82 (s, 1 H), 6.08 (s, 2 H), 5.05 (s, 2 H),4.18 (m, J = 7.2 Hz, 2 H), 3.97- 3.93 (m, 2 H), 1.70-1.20 (m, 9 H);LC-MS [M + H]⁺ 611.1 410

Benzyl 4-(2-{6-amino-8-[(6-bromo- 1,3-benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)piperidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ 8.63 (s,1 H), 7.47 (s, 1 H), 7.39- 7.25 (m, 6 H), 6.14 (s, 2 H), 5.06 (s, 2 H),4.31 (m, J = 7.2 Hz, 2 H), 3.97- 3.93 (m, 2 H), 1.70-1.20 (m, 9 H);LC-MS [M + H]⁺ 611.1 411

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-morpholin-4-ylethyl)- 9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.30 (s, 1 H), 7.39 (s, 1 H), 6.90(s, 1 H), 6.10 (s, 2 H), 4.58 (t, J = 6.0 Hz, 2 H), 3.60-3.50 (m, 4 H),3.40-3.30 (m, 4 H), 2.55-2.50 (m, 2 H); LC-MS [M + H]⁺ 479.3 412

tert-Butyl 2-(2-{6-amino-8-[(6- bromo-1,1-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ8.63(s, 1 H), 7.48 (s, 1 H), 7.34 (s, 1 H), 6.16 (s, 2 H), 4.30-4.20 (m, 2H), 3.30-3.20 (m, 2 H), 1.89-1.50 (m, 7 H), 1.24 (s, 9 H); TOF LC-MS[M + H]⁺ 563.0 413

tert-Butyl 3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)pyrrolidine-1- carboxylate. LC-MS TOF [M + H]⁺ 563.0414

tert-Butyl 2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)pyrrolidine-1- carboxylate. TOF LC-MS [M + H]⁺ 563.0415

tert-Butyl 3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-carboxylate. ¹H NMR (DMSO-d₆) δ8.22 (s, 1 H), 7.39 (s, 1 H), 6.88 (s, 1H), 6.09 (s, 2 H), 4.20-4.10 (m, 2 H), 3.30-3.20 (m, 2 H), 2.70-1.80 (m,7 H), 1.37 (s, 9 H); TOF LC-MS [M + H]⁺ 563.0 416

tert-Butyl (2S)-2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ 8.21(s, 1 H), 7.38 (s, 1 H), 6.73 (s, 1 H), 6.08 (s, 2 H), 4.20-3.80 (m, 2H), 2.51-2.45 (m, 2 H), 1.60-1.20 (m, 9 H), 1.30 (s, 9 H); LC-MS [M +H]⁺ 577.1 417

tert-Butyl (2S)-2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ8.49 (s,1 H), 7.41 (s, 1 H), 7.29 (s, 1 H), 6.11 (s, 2 H), 4.25-4.15 (m, 2 H),3.27-3.15 (m, 2 H), 1.60-1.20 (m, 9 H), 1.32 (s, 9 H); LC-MS [M + H]⁺577.1 418

tert-Butyl (3R)-3-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5- yl)thio]-9H-purin-9- yl}ethyl)pyrrolidine-1-carboxylate. ¹H NMR (DMSO-d₆) δ 8.24(s, 1 H), 7.37 (s, 1 H), 6.89 (s, 1 H), 6.08 (s, 2 H), 4.20-4.14 (m, 2H), 3.33-3.28 (m, 3 H), 2.00-1.70 (m, 6 H), 1.35 (s, 9 H); LC-MS [M +H]⁺ 564.8 419

Benzyl 2-(2-{6-amino-8-[(6-bromo- 1,3-benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (DMSO-d₆) 8.24 (s, 1H), 7.36 (s, 1 H), 7.32 (s, 1 H), 7.30-7.18 (m, 3 H), 6.88-6.82 (m, 2H), 6.07 (s, 2 H), 5.00 (s, 2 H), 4.20-4.10 (m, 2 H), 3.33-3.28 (m, 3H), 2.20-1.70 (m, 6 H); LC-MS [M + H]⁺ 599.1 420

tert-Butyl (3S)-3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ 8.60(s, 1 H), 7.45 (s, 1 H), 7.12 (s, 1 H), 6.14 (s, 2 H), 4.28 (t, J = 7.2Hz, 2 H), 3.40-3.30 (m, 3 H), 2.00-1.80 (m, 6 H), 1.36 (s, 9 H); LC-MS[M + H]⁺ 563.1 421

Benzyl 2-(2-{6-amino-8-[(6-bromo- 1,3-benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ8.67 (s,1 H), 7.47 (s, 1 H), 7.32 (s, 1 H), 7.40-7.18 (m, 5 H), 6.14 (s, 2 H),5.00 (s, 2 H), 4.29-4.27 (m, 2 H), 3.78-3.28 (m, 3 H), 2.20-1.70 (m, 6H); LC-MS [M + H]⁺ 599.1 422

1-tert-Butyl 2-ethyl cis-4-(2-{6- amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9 H-purin-9- yl}ethyl)piperidine-1,2-dicarboxylate. ¹H NMR (CD₃OD) δ8.31 (s, 1 H), 7.28 (s, 1 H), 7.17 (s, 1H), 6.09 (s, 2 H), 4.35-4.32 (m, 3 H), 4.17 (t, J = 7.2 Hz, 2 H), 3.68-3.60 (m, 1 H), 2.10-2.05 (m, 1 H), 1.92-1.80 (m, 4 H), 1.75-1.65 (m, # 1H), 1.42 (s, 9 H), 1.30-1.28 (m, 2 H), 1.23 (t, J = 7.2 Hz, 3 H); LC-MS[M + H]⁺ 649.1 423

1-tert-Butyl 2-ethyl cis-4-(2-{6- amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3 H-purin-3- yl}ethyl)piperidine-1,2-dicarboxylate. ¹H NMR (CD₃OD) δ8.48 (s, 1 H), 7.37 (s, 1 H), 7.34 (s, 1H), 6.15 (s, 2 H), 4.40-4.35 (m, 3 H), 4.18 (q, J = 7.2 Hz, 2 H), 3.68-3.60 (m, 1 H), 3.27-3.25 (m, 2 H), 2.20-1.70 (m, 6 H), 1.44 (s, 9 H), #1.26 (t, J = 7.2 Hz, 3 H); LC-MS [M + H]⁺ 649.1 424

9-[2-(1-Benzyl-1,2,3,6- tetrahydropyridin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9 H-purin-6-amine. ¹H NMR (CD₃OD) δ8.23 (s, 1 H), 7.52-7.45 (m, 5 H), 7.27 (s, 1 H), 7.16 (s, 1 H), 6.01(s, 2 H), 5.26 (s, 1 H), 4.60-4.30 (m, 4 H), 3.67-3.56 (m, 3 H), 3.50(m, 1 H), 2.72-2.52 (m, 4 H); LC-MS # [M + H]⁺ 565.8 425

3-[2-(1-Benzyl-1,2,3,6- tetrahydropyridin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 3 H-purin-6-amine. ¹H NMR (CD₃OD) δ8.49 (s, 1 H), 7.51-7.49 (m, 5 H), 7.36 (s, 1 H), 7.32 (s, 1 H), 6.13(s, 2 H), 5.42 (s, 1 H), 4.50 (brt, J = 6.4 Hz, 2 H), 4.39-4.43 (m, 2H), 3.64- 3.56 (m, 3 H), 3.21 (m, 1 H), 2.72 # (brt, J = 6.4 Hz, 2 H),2.57-2.52 (m, 2 H); LC-MS [M + H]⁺ 565.3 426

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]ethyl}-9 H-purin-6- amine. ¹H NMR (CD₃OD) δ8.26 (s, 1 H), 7.28 (s, 1 H), 7.15 (s, 1 H), 6.09 (s, 2 H), 4.34 (t, J =7.6 Hz, 2 H), 3.88-3.84 (m, 2 H), 2.77 (s, 3 H), 2.37-2.29 (m, 4 H),2.22-2.29 (m, 4 H), # 1.97-1.88 (m, 3 H); LC-MS [M + H]⁺ 517.1 427

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]ethyl}-3 H-purin-6- amine. ¹H NMR (CD₃OD) δ8.52 (s, 1 H), 7.39 (s, 1 H), 7.36 (s, 1 H), 6.16 (s, 2 H), 4.40 (m, 2H), 3.89-3.85 (m, 2 H), 2.78 (s, 3 H), 2.37-2.30 (m, 4 H), 2.25 (q, J =7.6 Hz, 2 H), 2.15- # 2.13 (m, 2 H), 1.94 (brd, J = 14.8 Hz, 2 H), 1.90(m, 1 H); LC-MS [M + H]⁺ 517.1 428

tert-Butyl trans-4-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-2- isopropylpiperidine-1-carboxylate. ¹HNMR (CD₃OD) δ 8.18 (s, 1 H), 7.25 (s, 1 H), 7.06 (s, 1 H), 6.07 (s, 2H), 4.29 (td, J = 7.6, 2.8 Hz, 2 H), 3.75 (dd, J = 13.6, 7.6 Hz, 1 H),3.52 (q, J = 8.8 Hz, 1 H), 2.91 (ddd, # J = 13.6, 11.2, 6.8 Hz, 1 H),1.96 (m, 1 H), 1.89-1.76 (m, 4 H), 1.40 (s, 9 H), 1.32 (m, 1 H),1.23-1.14 (m, 2 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.86 (d, J = 6.8 Hz, 3H); LC-MS [M + H]⁺ 619.1 429

tert-Butyl cis-4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)-2- isopropylpiperidine-1-carboxylate. ¹H NMR (CD₃OD)δ 8.17 (s, 1 H), 7.25 (s, 1 H), 7.06 (s, 1 H), 6.07 (s, 2 H), 4.33-4.25(m, 2 H), 3.99 (brt, J = 13.6 Hz, 1 H), 3.76 (m, 1 H), 2.75 and 2.67(two brt, J = 14 and 13.6 # Hz, 1 H), 1.96-1.89 (m, 2 H), 1.79- 1.61 (m,4 H), 1.44 (s, 9 H), 1.19- 1.02 (m, 2 H), 0.92-0.88 (m, 3 H), 0.81 and0.78 (two d, J = 6.4 and 6.8 Hz, 3 H); LC-MS [M + H]⁺ 619.1 430

tert-Butyl cis-4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)-2- isopropylpiperidine-1-carboxylate. ¹H NMR (CD₃OD)δ 8.52 (s, 1 H), 7.36 (s, 1 H), 7.35 (s, 1 H), 6.15 (s, 2 H), 4.41 (t, J= 7.6 Hz, 2 H), 4.05 (brt, J = 12.8 Hz, 1 H), 3.78 (m, 1 H), 2.81 and2.72 (two brt, J = 12.8 and # 12.4 Hz, 1 H), 2.03 (m, 1 H), 1.93 (brd, J= 12.4 Hz, 1 H), 1.83-1.72 (m, 4 H), 1.46 (s, 9 H), 1.22-1.04 (m, 2 H),0.95-0.92 (m, 3 H), 0.84 and 0.81 (two d, J = 6.8 and 6.8 Hz, 3 H);LC-MS [M + H]⁺ 619.1 431

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-N-ethylpiperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.29 (s, 1H), 7.28 (s, 1 H), 7.18 (s, 1 H), 6.08 (s, 2 H), 4.36 (t, J = 7.4 Hz, 2H) 3.97 (br d, J = 13.2 Hz, 2 H), 3.16 (q, J = 7.0 Hz, 2 H), 2.69 (t, J= 10.5 Hz, 2 H), 1.85-1.76 (m, # 4 H), 1.58-1.46 (m, 1 H), 1.22-1.13 (m,2 H), 1.09 (t, 7.03 Hz, 3 H); TOF LC-MS [M + H]⁺ 548.1 432

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-N-isopropylpiperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.31 (s,1 H), 7.28 (s, 1 H), 7.2 (s, 1 H), 6.09 (s, 2 H), 4.36 (t, J = 7.4 Hz, 2H), 4.01 (br d, J = 13.2 Hz, 2 H), 3.87 (q, J = 6.2 Hz, 1 H), 2.70 (t, J= 10.9 Hz, 2 H), 1.84-1.76 (m, # 4 H), 1.68-1.46 (m, 1 H), 1.20-1.00 (m,8 H); TOF LC-MS [M + H]⁺ 562.1 433

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-N-(tert-butyl)piperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.30(s, 1 H), 7.28 (s, 1 H), 7.19 (s, 1 H), 6.08 (s, 2 H), 4.36 (t, J = 7.4Hz, 2 H), 3.95 (broad d, J = 13.6 Hz, 2 H), 2.67 (dt, J = 2.3, 12.8 Hz,2 H), 1.85-1.75 # (m, 4 H), 1.59-1.43 (m, 1 H), 1.31 (s, 9 H), 1.22-1.05(m, 2 H); TOF LC-MS [M + H]⁺ 576.1 434

Ethyl N-{[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1- yl]carbonyl}glycinate. ¹H NMR (CD₃OD) δ8.33 (s, 1 H), 7.28 (s, 1 H), 7.21 (s, 1 H), 6.09 (s, 2 H), 4.37 (t, J =7.0 Hz, 2 H), 4.16 (q, J = 7.0 Hz, 2 H), 4.01 (broad d, J = 13.2 Hz, 2H), 3.83 (s, # 2 H), 2.78 (t, J = 12.1 Hz, 2 H), 1.86-1.79 (m, 4 H),1.61- 1.48 (m, 1 H), 1.33-1.18 (m, 5 H); TOF LC-MS [M + H]⁺ 606.1 435

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-N-ethylpiperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.31 (s, 1H),7.27 (s, 1 H), 7.22 (s, 1 H), 6.09 (s, 2 H), 4.38 (t, J = 7.4 Hz, 2H), 3.97-3.89 (m, 1 H), 3.78 (d, J = 7.0 Hz, 1 H), 3.16 (q, J = 7.0 Hz,2 H), 2.85 (dt, J = 11.3, 2.7 Hz, 1 H), # 2.61 (dd, J = 13.2, 10.1 Hz, 1H), 2.05-1.96 (m, 1 H), 1.86 (sext, J = 7.4 Hz, 1 H), 1.78-1.62 (m, 2H), 1.60-1.20 (m, 3 H), 1.08 (t, J = 7.0 Hz, 3 H); TOF LC-MS [M + H]⁺548.1 436

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-N-isopropylpiperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.30 (s,1 H), 7.28 (s, 1 H), 7.22 (s, 1 H), 6.09 (s, 2 H), 4.38 (t, J = 7.4 Hz,2 H), 3.97-3.77 (m, 3 H), 2.84 (dd, J = 11.3, 3.1 Hz, 1 H), 2.60 (dd, J= 13.2, 10.1 Hz, 1 H), 2.04-1.97 # (m, 1 H), 1.92-1.82 (m, 1 H), 1.78-1.63 (m, 3 H), 1.59-1.40 (m, 2 H), 1.12 (dd, J = 6.6, 2.7 Hz, 6 H); TOFLC-MS [M + H]⁺ 562.1 437

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9 H-purin-9-yl}ethyl)-N-(tert-butyl)piperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.30(s, 1 H), 7.28 (s, 1 H), 7.22(s, 1 H), 6.09 (s, 2 H), 4.38 (t, J = 7.0Hz, 2 H), 3.92-3.86 (m, 1 H), 3.79- 3.72 (m, 1 H), 2.81 (dt, J = 14.0,3.1 Hz, 1 H), 2.55 (dd, J = 13.2, 10.1 # Hz, 1 H), 2.04-1.95 (m, 1 H),1.85 (p, J =5.8 Hz, 1 H), 1.75-1.64 (m, 2 H), 1.54-1.40 (m, 2 H),1.31-1.18 (m, 10 H); TOF LC-MS [M + H]⁺ 576.1 439

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)-N-ethylpiperidine-1- carboxamide. TOF LC-MS [M + H]⁺ 548.1 439

4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)-N-isopropylpiperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.52 (s,1 H), 7.37 (s, 1 H), 7.35 (s, 1 H), 6.15 (s, 2 H), 4.42 (t, J = 7.03 Hz,2 H), 4.01 (d, J = 12.8 Hz, 2 H), 3.92-3.84 (m, 1 H), 2.72 (t, J = 13.2Hz, 2 H), 1.92-1.83 (m, 2 H), 1.80- # 1.70 (m, 2 H), 1.68-1.48 (m, 3 H),1.43 (d, J = 6.6 Hz, 3 H), 0.97 (d, J = 6.6 Hz, 3 H); TOF LC-MS [M + H]⁺562.1 440

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)-N-ethylpiperidine-1- carboxamide. TOF LC-MS [M + H]⁺ 548.1 441

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)-N-isopropylpiperidine-1- carboxamide. TOF LC-MS [M + H]⁺ 562.1442

3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)-N-(tert-butyl)piperidine-1- carboxamide. ¹H NMR (CD₃OD) δ8.53(s, 1 H), 7.37 (s, 1 H), 7.36 (s, 1 H), 6.14 (s, 2 H), 4.43 (t, J = 7.8Hz, 2 H), 3.90-3.85 (m, 1 H), 3.79- 3.72 (m, 1 H), 2.83 (tt, J = 10.9,3.1 Hz, 1 H), 2.54 (dd, J = 13.2, 10.1 # Hz, 1 H), 1.97-1.78 (m, 3 H),1.71- 1.63 (m, 1 H), 1.50-1.38 (m, 2 H), 1.33-1.16 (m, 10 H); TOF LC-MS[M + H]⁺ 576.1 443

Ethyl N-{[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidin-1- yl]carbonyl}glycinate. ¹H NMR (CD₃OD) δ8.54 (s, 1 H), 7.36 (s, 1 H), 6.15 (s, 2 H), 4.42 (t, J = 7.81 Hz, 2 H),4.16 (q, J = 7.0 Hz, 2 H), 3.99 (broad d, J = 13.2 Hz, 2 H), 3.84 (s, 2H), 2.79 (t, J = 11.3 # Hz, 2 H), 1.88 (q, J = 7.4 Hz, 2 H), 1.76 (d, J= 12.5 Hz, 2 H), 1.62-1.50 (m, 1 H), 1.35-1.16 (m, 5 H); TOF LC-MS [M +H]⁺ 606.1 444

8-[(2,5-Dimethoxyphenyl)thio]-9- {2-[4-(2,2-dimethylpropanoyl)piperazin-1- yl]ethyl}-9 H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.32 (s, 1 H), 7.07 (d, J = 2.8 Hz, 1 H), 7.04 (s, 1 H), 7.01(dd, J = 14.4, 2.8 Hz, 1 H), 4.70 (t, J = 6.0 Hz, 2 H), 3.91-3.80 (m, 4H), 3.75 (s, 6 H), 3.42 (t, J = 6.0 # Hz, 2 H), 3.24-3.180 (m, 4 H),1.29 (s, 9 H); TOF LC-MS LC-MS [M + H]⁺ 500.3 445

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-isopropylpiperidin-2-yl)ethyl]-9 H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.23 (s, 1 H), 7.30 (s,1 H), 7.14 (s, 1 H), 6.09 (s, 2 H), 4.42-4.20 (m, 2 H), 4.20-4.00 (m, 1H), 2.97-2.94 (m, 2 H), 2.50-2.30 (m, 2 H), 2.10-1.90 (m, 4 H), 1.75-1.70 (m, 2 H), 1.65-1.59 (m, 1 H), # 1.38 (d, J = 6.8 Hz, 3 H). 1.21 (d,J = 6.8 Hz, 3 H); LC-MS [M + H]⁺ 519.1 446

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(1-isopropylpiperidin-2-yl)ethyl]-3 H-purin-6-amine ¹H NMR (CD₃OD) δ 8.51 (s, 1 H), 7.40 (s, 1H), 7.31 (s, 1 H), 6.09 (s, 2 H), 4.52-4.45 (m, 2 H), 4.10-4.00 (m, 1H), 3.60-3.50 (m, 2 H), 2.97-2.92 (m, 2 H), 2.24-2.20 (m, 2 H), 2.00-1.90 (m, 2 H), 1.76-1.71 (m, 2 H), # 1.62-1.60 (m, 1 H), 1.40 (d, J =6.4 Hz, 3 H). 1.24 (d, J = 6.8 Hz, 3 H); LC-MS [M + H]⁺ 519.1 447

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-isobutylpiperidin-2-yl)ethyl]-9 H-purin-6-amine ¹H NMR (CD₃OD) δ 8.28 (s, 1 H), 7.30 (s, 1H), 7.20 (s, 1 H), 6.10 (s, 2 H), 4.80-4.30 (m, 2 H), 3.65-3.62 (m, 1H), 3.12-3.11 (m, 2 H), 2.93-2.87 (m, 2 H), 2.32-2.10 (m, 2 H), 2.10-1.90 (m, 4 H), 1.81-1.72 (m, 2 H), # 1.67-1.61 (m, 1 H). 1.07-1.02 (m, 6H); LC-MS [M + H]⁺ 533.3 448

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(1-isobutylpiperidin-2-yl)ethyl]-3 H-purin-6-amine ¹H NMR (CD₃OD) δ 8.52 (s, 1 H), 7.40 (s, 1H), 7.30 (s, 1 H), 6.20 (s, 2 H), 4.47-4.45 (m, 2 H), 3.48-3.43 (m, 1H), 3.30-3.10 (m, 2 H), 3.00-2.90 (m, 2 H), 2.65 (m, 1 H), 2.32-2.30 (m,2 H), 2.20-2.10 (m, 2 H), 1.90- # 1.80 (m, 2 H), 1.62-1.60 (m, 2 H).1.11-1.10 (m, 6 H); LC-MS [M + H]⁺ 533.3 449

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(2,2-dimethylpropanoyl)piperidin-3- yl[ethyl}-9 H-purin-6-amine ¹H NMR(CD₃OD) δ 8.30 (s, 1 H), 7.30 (s, 1 H), 7.20 (s, 1 H), 6.10 (s, 2 H),4.40 (t, J = 7.2 Hz, 2 H), 4.20-4.10 (m, 2 H), 3.10-3.00 (m, 1 H), 2.80-2.70 (m, 2 H), 2.10-1.90 (m, 2 H), # 1.80-1.70 (m, 2 H), 1.53-1.50 (m, 2H), 1.24 (m, 9 H); LC-MS [M + H]⁺ 561.1 450

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[1-(2,2-dimethylpropanoyl)piperidin-3- yl]ethyl}-3 H-purin-6-amine ¹H NMR(CD₃OD) δ 8.53 (s, 1 H), 7.38 (s, 1 H), 7.36 (s, 1 H), 6.20 (s, 2 H),4.50 (t, J = 7.2 Hz, 2 H), 4.20-4.10 (m, 2 H), 3.14-3.12 (m, 2 H), 2.80-2.70 (m, 2 H),2.00-1.93 (m, 1 H), # 1.93-1.90 (m, 2 H), 1.50-1.49 (m, 2H), 1.30 (m, 9 H); LC-MS [M + H]⁺ 561.1 451

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(2,2-dimethylpropanoyl)piperidin-4- yl]ethyl}-9 H-purin-6-amine ¹H NMR(CD₃OD) δ 8.20 (s, 1 H), 7.30 (s, 1 H), 7.10 (s, 1 H), 6.10 (s, 2 H),4.40 (d, J = 14 Hz, 2 H), 4.30 (t, J = 7.6 Hz, 2 H), 2.80 (s, 2 H),1.90-1.84 (m, 2 H), 1.80-1.70 (m, 2 H), 1.64- # 1.60 (m, 1 H), 1.30 (s,9 H), 1.20- 1.10 (m, 2 H); LC-MS [M + H]⁺ 561.1 452

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[1-(2,2-dimethylpropanoyl)piperidin-4- yl]ethyl}-3 H-purin-6-amine ¹H NMR(CD₃OD) δ 8.52 (s, 1 H), 7.40 (s, 1 H), 7.30 (s, 1 H), 6.10 (s, 2 H),4.44-4.40 (m, 2 H), 2.90-2.80 (m, 2 H), 1.90-1.88 (m, 2 H), 1.80- 1.70(m, 2 H), 1.70-1.60 (m, 2 H), # 1.60-1.50 (m, 1 H), 1.30 (s, 9 H),1.20-1.10 (m, 2 H); LC-MS LC-MS [M + H]⁺ 561.1 453

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-isobutylpiperidin-4-yl)ethyl]-9 H-purin-6-amine ¹H NMR (CD₃OD) δ 8.22 (s, 1 H), 7.30 (s, 1H), 7.10 (s, 1 H), 6.10 (s, 2 H), 4.40 (t, J = 7.2 Hz, 2 H), 3.60- 3.58(m, 2 H), 3.00-2.90 (m, 2 H), 2.15-2.10 (m, 2 H), 2.00-1.90 (m, 2 H),1.90-1.80 (m, 2 H), 1.60-1.50 # (m, 2 H), 1.30-1.20 (m, 2 H), 1.10- 1.00(m, 6 H); LC-MS [M + H]⁺ 533.1 454

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(3,3-dimethylbutanoyl)piperidin-3- yl]ethyl}-9 H-purin-6-amine ¹H NMR (CD₃OD)δ 8.30 (s, 1 H), 7.30 (s, 1 H), 7.20 (s, 1 H), 6.10 (s, 2 H), 4.40-4.36(m, 2 H), 4.30-4.27 (m, 1 H), 4.00-3.90 (m, 1 H), 2.70-2.60 (m, 1 H),2.40-2.20 (m, 2 H), 2.00- 1.90 (m, 2 H), 1.80-1.70 (m, 2 H), # 1.50-1.40(m, 2 H), 1.40-1.30 (m, [M + H]⁺ 575.1 455

tert-Butyl [trans-4-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5-yl)thio]-9 H-purin-9- yl}ethyl)cyclohexyl]carbamate. NMR (CD₃OD) δ 8.26(s, 1 H), 7.28 (s, 1 H), 7.15 (s, 1 H), 6.08 (s, 2 H), 4.31 (t, J = 8.4Hz, 2 H), 3.35-3.25 (m, 2 H), 1.91-0.83 (m, 19 H). TOF- MS [M + H]⁺591.1 456

tert-Butyl (2S)-2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (CD₃OD) δ8.24 (s,1 H), 7.27 (s, 1 H), 7.11 (s, 1 H), 6.08 (s, 2 H), 4.36-4.28 (m, 2 H),4.00-3.86 (m, 2 H), 3.36-3.25 (m, 3 H), 2.00-0.80 (m, 13 H). TOF- MS[M + H]⁺ 563.0 457

tert-Butyl (2S)-2-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (CD₃OD) δ8.59 (s,1 H), 7.37 (s, 1 H), 7.36 (s, 1 H), 6.15 (s, 2 H), 4.42-4.38 (m, 2 H),3.86-3.78 (m, 2 H), 3.36-3.25 (m, 3 H), 1.90-0.80 (m, 13 H). TOF- MS[M + H]⁺ 563.0 458

tert-Butyl 3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)azetidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ 8.23 (s,1 H), 7.37 (s, 1 H), 6.90 (s, 1 H), 6.08 (s, 2 H), 4.12 (t, J = 6.4 Hz,2 H), 3.80- 3.60 (m, 2 H), 3.55-3.46 (m, 1 H), 2.50-2.45 (m, 2 H),2.00-1.96 (m, 2 H), 1.33 (s, 9 H); LC-MS # [M + H]⁺ 549.2 459

tert-Butyl 3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)azetidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ 8.57 (s,1 H), 7.48 (s, 1 H), 7.38 (s, 1 H), 6.15 (s, 2 H), 4.23 (t, J = 6.8 Hz,2 H), 3.90-3.80 (m, 2 H), 3.66- 3.60 (m, 1 H), 2.50-2.45 (m, 2 H),2.11-2.00 (m, 2 H), 1.34 (s, 9 H). LC- # MS [M + H]⁺ 549.2 460

tert-Butyl (3S)-3-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)pyrrolidine-1- carboxylate. ¹H NMR (DMSO-d₆) δ8.23(s, 1 H), 7.37 (s, 1 H), 6.86 (s, 1 H), 6.08 (s, 2 H), 4.20-4.10 (m, 2H), 3.20-3.00 (m, 2 H), 2.50-2.00 (m, 4 H), 2.00-1.70 (m, 3 H), 1.35 (s,9H). LC-MS [M + H]⁺ 564.2 461

tert-Butyl (3R)-3-(2-{6-amino-8- [(6-bromo-1,3-benzodioxol-5- yl)thio]-3H-purin-3- yl}ethyl)pyrrolidine-1-carboxylate. ¹H NMR (DMSO-d₆) δ 8.62(s, 1 H), 7.47 (s, 1 H), 7.35 (s, 1 H), 6.15 (s, 2 H), 4.35-4.20 (m, 2H), 3.20-3.00 (m, 2 H), 2.80-2.70 (m, 2 H), 2.00- 0.80 (m, 14 H). LC-MS[M + H]⁺ 564.2 462

tert-Butyl 5-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)-3,4- dihydropyridine-1(2 H)- carboxylate. ¹H NMR(CD₃OD) δ 8.29 (s, 1 H), 7.28 (s, 1 H), 7.18 (s, 1 H), 6.09 (s, 2 H),6.34 and 6.05 (s, 1 H), 4.38 (m, 2 H), 3.45-3.35 (m, 2 H), 2.59-2.51 (m,2 H), 2.20-2.17 (m, 2 H), 1.84-1.77 (m, 2 H), 1.43 # and 1.36 (s, 9 H);LC-MS [M + H]⁺ 575.6. 463

tert-Butyl 5-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)-3,4- dihydropyridine-1(2 H)- carboxylate. ¹H NMR(CD₃OD) δ 8.46 (s, 1 H), 7.39 (s, 1 H), 7.37 (s, 1 H), 6.30 and 6.06 (s,1 H), 6.16 (s, 2 H), 4.47 (t, J = 6.8 Hz, 2 H), 3.45- 3.36 (m, 2 H),2.62-2.52 (m, 2 H), 2.16-2.09 (m, # 2 H), 1.80 (t, J = 6.8 Hz, 2 H),1.37 (s, 9 H); LC-MS [M + H]⁺ 575.0 464

tert-Butyl 4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)-3,3- dimethylpiperidine-1-carboxylate. ¹H NMR(CDCl₃) δ 8.26 (s, 1 H), 7.14 (s, 1 H), 6.99 (s, 1 H), 6.05 (s, 2 H),4.30-4.19 (m, 3 H), 3.61 (m, 1 H), 2.63 (m, 1 H), 2.40 (m, 1 H), 2.07(m, 1 H), 1.78 (m, 1 H), 1.45 (s, 9 H), 1.40- # 1.32 (m, 2 H), 1.14 (m,1 H), 0.79 (s, 3 H), 0.76 (s, 3 H),; TOF-MS [M + H]⁺ 605.15

Example 465 Synthesis of8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-4-ylethyl)-9H-purin-6-amine

To a solution of tert-Butyl4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate(0.030 g) in DCM (10 mL) was added trifluoroacetic acid (5 mL) at roomtemperature and stirring was continued at rt for 1-16 h. The solvent andthe excess trifluoroacetic acid was evaporated to dryness. The oilyresidue was co-evaporated with toluene (3×5 mL) to afford title productas a trifluoroacetate salt. ¹H NMR (DMSO-d₆) δ 8.21 (s, 1H), 7.40 (s,1H), 6.85 (s, 1H), 6.10 (s, 2H), 4.19 (t, J=7.6 Hz, 2H), 3.25-3.20 (m,2H), 2.80-2.75 (m, 2H), 1.88-1.85 (m, 2H), 1.68-1.62 (m, 2H), 1.50-1.42(M, 1H), 1.30-1.24 (m, 2H); LC-MS [M+H]⁺ 477.1

Example 466 Synthesis of8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-3-ylethyl)-9H-purin-6-amine

To a suspension of tert-Butyl3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate(0.03 g) in ethyl acetate (10 mL) was added 6N HCl (5 mL) at roomtemperature and stirring was continued at rt for 1-16 h. The solvent andthe excess hydrochloric acid was evaporated to dryness. The oily residuewas co-evaporated with toluene (3×5 mL) to afford title product ashydrochloride salt. ¹H NMR (CD₃OD) δ 8.38 (s, 1H), 7.29 (s, 1H), 7.26(s, 1H), 6.10 (s, 2H), 4.43-4.41 (m, 2H), 3.49-3.46 (m, 1H), 2.95-2.92(m, 1H), 2.80-2.65 (m, 2H), 1.92-1.76 (m, 4H), 1.39-1.23 (m, 4H); TOFLC-MS [M+H]+] 477.1

Examples 467-472 and examples 479 and 480 were synthesized analogouslyto the procedure described for example 465 using appropriate startingmaterials from table 7 and isolated as a trifluoroacetate salts andtheir analytical data summarized in Table 8. Examples 473-478 andexamples 481-484 were synthesized analogously to the procedure describedfor example 466 and isolated as HCl salts, and their analytical datasummarized in table 8. TABLE 8 Name and Analytical Example No. StructureData 467

8-[(2,5- Dimethoxyphenyl)thio]- 3-(2-piperidin-4-ylethyl)-3H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.60 (s, 1H), 8.40(m, 1H),8.20-8.10(m 2H) 4.34-4.32(m, 2H), 3.76(s, 3H), 3.71(s, 3H), 3.60-3.30(m,4H), 3.27-3.23 (m, 3H), 1.90-1.80(m, 2H), 1.3 1-1.25(m, 2H); LC-MS [M +H]⁺ 415.1 468

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-3- (2-piperidin-4-ylethyl)-3H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.55 (s, 1H), 7.46(s, 1H), 7.30(s,1H), 6.15(s, 2H), 4.31(t, J=7.2 Hz, 2H), 3.26-3.23(m, 2H), 2.90-2.80(m,2H), 1.88-1.81(m, 4H), 1.30-1.20 (m, 3H); LC-MS [M + H]⁺ 477.1 469

8-[(2,5- Dimethoxyphenyl)thio]- 9-(2-piperidin-4-ylethyl)-9H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.23(s, 1H), 7.04(d, J=9.2 Hz, 1H),6.88(dd, J=9.2, 2.8Hz, 1H), 6.48 (d, J=2.8 Hz, 1H), 4.20 (t, J=7.2Hz,2H), 3.77 (s, 3H), 3.62(s, 3H), 3.23-3.20(m, 4H), 2.70-2.58(m, 1H),1.85-1.78 (m, 2H), 1.65-1.60(m, 2H), 1.28-1.20(m, 2H); LC-MS [M + H]⁺415.1 470

8-[(2,5- Dimethoxyphenyl)thio]- 9-(2-piperidin-3-ylethyl)-9H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.21 (s, 1H), 7.05(d, J=8.8 Hz, 1H),6.80(dd, J=8.8, 2.4Hz, 1H), 6.46(d, J=2.4Hz, 1H), 4.22-4.20 (m, 2H),3.77(s, 3H), 3.61(s, 3H), 2.52-2.45 (m, 7H), 1.70-1.30(m, 4H); LC-MS[M + H]^(+415.1) 471

8-[(6-Bromo-1,3- benzodioxol-5 -yl)thio]-9- (2-piperidin-4-ylideneethyl)-9H-purin- 6-amine. ¹H NMR (CD₃OD) δ 8.35(s, 1H), 7.29(s,1H), 7.25(s, 1H), 6.10(s, 2H), 5.39 (s, 1H), 4.47(t, J=7.2 Hz, 2H),3.52(brs, 2H), 3.35-3.30(m, 2H), 2.66 (t, J=7.2 Hz, 2H), 2.55-2.49(m,2H), 1.44(s, 9H); LC-MS [M + H]^(+475.0) 472

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- [2-(3,3- dimethylpiperidin-4-yl)ethyl]-9H-purin-6- amine ¹H NMR(CDCl₃) δ 8.29 (s, 1H), 7.29(s, 1H),7.17(s, 1H), 6.09(s, 2H), 4.38-4.32(m, 2H), 3.78(m, 1H), 3.01(d, J=12.4Hz, 1H), 2.91(brt, J=13.2 Hz, 1H), 2.74(d, J=12.4 Hz, 1H), 2.20 (m, 2H),1.63(m, 1H), 1.54-1.38(m, 2H), 0.97 (s, 3H), 0.93(s, 3H); TOF-MS [M +H]⁺ 505.15 473

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[(3R)-piperidin-3-yl]ethyl}-9H-purin-6- amine. LC-MS [M + H]^(+477.1) 474

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[(3S)-piperidin-3-yl]ethyl}-9H-purin-6- amine. ¹H NMR (Acetone-d₆) δ 8.37(s, 1H), 7.27(s,1H), 7.01 (s, 1H), 6.13(s, 2H), 4.45-4.40(m, 2H), 3.70-3.60(m, 2H),1.90-1.50 (m, 9H); TOF LC-MS [M + H]⁺ 477.4 475

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[(2R)-piperidin-2-yl]ethyl}-9H-purin-6- amine. TOF LC-MS [M + H]⁺ 477.1 476

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- (2-pyrrolidin-3-ylethyl)-9H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.33 (s, 1H), 7.42(s, 1H), 6.97(s,1H), 6.12(s, 2H), 4.22(t, J=7.6 Hz, 2H), 3.18-3.14(m, 2H), 1.56-1.23(m,7H). 477

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[(2S)-piperidin-2-yl]ethyl}-9H-purin-6- amine.¹H NMR(CD₃OD) δ 8.40(s, 1H), 7.29(s, 1H),7.27(s, 1H), 6.10 (s, 2H), 4.55-4.44(m, 2H), 3.10-2.90(m, 2H),2.30-1.50(m, 8H); LC- MS [M + H]⁺ 477.1 478

8-[(6-Bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[(3R)-pyrrolidin-3-yl]ethyl}-9H-purin-6- amine. ¹H NMR (CD₃OD) δ 8.37(s, 1H), 7.30(s, 1H),7.27(s, 1H), 6.10(s, 2H), 4.41(t, J=6.8Hz, 2H), 3.58-3.48 (m, 2H),3.33-3.28(m, 1H), 2.95-2.90(m, 2H), 2.35-2.30(m, 2H), 2.13-2.01(m, 2H),1.74-1.72 (m, 2H); LC-MS [M + Na]⁺ 480.0 479

8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[trans-2-isopropylpiperidin-4- yl]ethyl}-9H-purin-6- amine. ¹H NMR (CD₃OD) δ8.32(s, 1H), 7.29(s, 1H), 7.21(s, 1H), 6.10(s, 2H), 4.29 (td, J=7.6, 3.2Hz, 2H), 3.41(ddd, J=13.2, 4.0, 2.0 Hz, 1H), 2.99(td, J=13.2, 3.2 Hz,1H), 2.90 # (ddd, J=12.0, 5.6, 2.8, 2H), 2.18(br d, J=14.0 Hz, 1H),2.08(br d, J=14.4 Hz, 1H), 1.97-1.83 (m, 3H), 1.63(m, 1H), 1.41(qd,J=13.2, 4.4 1H), 1.16(q, J=12.4 Hz, 1H), 1.05(d, J=6.8 Hz, 3H), 1.03(d,J=6.8 Hz, 3H); LC-MS [M + H]^(+519.3) 480

8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9- {2-[cis-2-isopropylpiperidin-4- yl]ethyl}-9H-purin-6- amine. ¹H NMR (CD₃OD) δ8.29(s, 1H), 7.29(s, 1H), 7.18(s, 1H), 6.09(s, 2H), 4.36 (m, 2H),3.23-3.19(m, 2H), 3.10(m, 1H), 2.02-1.91(m, 5H), 1.83-1.74 (m, 3H),1.04(d, J=6.8 Hz, 3H), 1.01(d, J=6.4 Hz, 3H); LC-MS [M + H]^(+519.3) 481

9-[2-(cis-4- Aminocyclohexyl)ethyl]8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.17 (s,1H), 7.37(s, 1H), 6.83(s, 1H), 6.08(s, 2H), 4.15(t, J=7.2Hz, 2H),3.20-3.10(m, 2H), 2.50-2.40(m, 2H), 1.70-1.35(m, 10H). TOF-MS [M + H]⁺491.0 482

Ethyl cis-4-(2-{6-amino- 8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3- yl}ethyl)piperidine-2- carboxylate. ¹H NMR (CD₃OD) δ 8.56(s,1H), 7.39(s, 1H), 7.37(s, 1H), 6.16(s, 2H), 4.48(t, J=6.8 Hz, 2H),4.33(q, J=7.2 Hz, 2H), 4.05-4.00(m, 1H), 3.55-3.46 (m, 1H), 3.12-3.00(m,1H), 2.55-2.44(m, 1H), 2.14-1.70(m, 4H), 1.50-1.30(m, 2H), 1.34(t, J=7.2Hz, 3H). LC-MS # [M + H]⁺ 549.1 483

9-(2-Azetidin-3-ylethyl)-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 9.19(s, 1H), 8.21(s, 1H), 7.82(s, 1H),6.02(s, 2H), 4.96(t, J=7.2 Hz, 2H), 4.70-4.60(m, 2H), 3.55-3.46(m, 1H),3.35-3.25(m, 2H), 2.92-2.87(m, 2H). LC-MS [M + H]⁺ 449.3 484

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[(3S)-pyrrolidin-3-yl]ethyl}-9H-purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.29(s, 1H), 7.39(s, 1H),6.93(s, 1H), 6.10(s, 2H), 4.19(t, J=8.4 Hz, 2H), 3.60-3.00(m, 6H),2.50-2.00(m, 3H). LC-MS [M + H]⁺ 464.92

Examples 485 and 4861-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-2,6-dioneand 8-(2,5-dimethoxy-phenylsulfonyl)-9-vinyl-9H-purin-6-ylamine

Title compounds were prepared in two steps reaction sequence asdescribed below:

Step 1: Synthesis of9-(bromo-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine

A mixture of 8-(2,5-dimethoxyphenylthio)-9H-purin-6-amine (1.00 g, 3.30mmol), 1,3-dibromoethane (1.42 mL, 16.48 mmol), and Cs₂CO₃ (1.29 g, 3.96mmol) in DMF (11 mL) was stirred for 1-2 days at room temperature. Thereaction mixture was then diluted with CH₂Cl₂, washed with brine, dried(Na₂SO₄), filtered, and concentrated in vacuo. After standing for 10 h,the mixture was treated with CH₂Cl₂. The resulting solid was filtered,washed with EtOAc, and air-dried to afford the product (274 mg, 20%).The combined filtrates were concentrated and purified by columnchromatography (CH₂Cl₂/EtOAc/MeOH=1/1/0.1 to 1/1/0.5) to give additionalproduct (200 mg, 15%): ¹H NMR (DMSO) δ 8.18 (s, 1H), 7.95 (brs, 2H),7.02 (d, J=8.8 Hz, 1H), 6.87 (dd, J=8.8, 3.2 Hz, 1H), 6.57 (d, J=3.2 Hz,1H), 4.61 (t, J=6.0 Hz, 2H), 3.86 (t, J=6.0 Hz, 2H), 3.76 (s, 3H), 3.62(s, 3H); TOF LC-MS [M+H]⁺ 410.0. When the reaction was carried out athigh temperature 85-90° C. otherwise identical reaction conditions gavea 1:1 mixture of N9 and N3 isomers.

Step 2: Coupling of Step 1 Product with Glutamide

A solution of glutamide (10 mg, 0.091 mmol) in DMF (0.5 mL) was treatedwith NaH (4.3 mg, 0.11 mmol) at room temperature. After stirring for 15min, a solution of step 1 intermediate (N-9) (34 mg, 0.083 mmol) in DMF(1 mL) was added dropwise to the solution of glutamide anion. Theresulting mixture was heated at 60° C. for 10 h, cooled to roomtemperature and quenched with AcOH (10 μL). The reaction mixture wasextracted with EtOAc, washed with brine, dried (Na₂SO₄), filtered, andconcentrated in vacuo. The crude material was purified by preparativeHPLC to afford the desired compound (8 mg) along with the eliminationproduct 8-(2,5-dimethoxy-phenylsulfonyl)-9-vinyl-9H-purin-6-ylamine (10mg).1-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-2,6-dione.¹H NMR (CD₃OD) δ 8.30 (s, 1H), 7.10 (d, J=2.8 Hz, 1H), 7.06 (d, J=8.8Hz, 1H), 7.02 (dd, J=8.8, 2.8 Hz, 12H), 4.54-4.50 (m, 2H), 4.24-4.22 (m,2H), 3.78 (s, 3H), 3.75 (s, 3H), 2.57 (t, J=6.8 Hz, 4H), 1.89 (quintet,J=6.8 Hz, 2H); TOF-MS [M+H]⁺ 443.1.8-(2,5-dimethoxy-phenylsulfonyl)-9-vinyl-9H-purin-6-ylamine. ¹H NMR(DMSO-d₆) δ 8.24 (s, 1H), 7.57 (dd, J=15.6, 8.8 Hz, 1H), 7.03 (d, J=9.2Hz, 1H), 6.87 (dd, J=9.2, 3.2 Hz, 1H), 6.43 (d, J=3.2 Hz, 1H), 6.39 (d,J=15.6 Hz, 1H), 5.24 (d, J=8.8 Hz, 1H), 3.76 (s, 3H), 3.61 (s, 3H).

Examples 487 and 4888-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(4-isopropylpiperazin-1-yl)ethyl]-9H-purin-6-amineand8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(4-isopropylpiperazin-1-yl)ethyl]-3H-purin-6-amine

Title compounds were prepared in two steps reaction sequence asdescribed below:

Step 1:_Synthesis8-(6-bromo-benzo[1,3]dioxol-5-ylsulfonyl)-9-(2-bromo-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfonyl)-3-(2-bromo-ethyl)-3H-purin-6-ylamine

The title compounds8-(6-bromo-benzo[1,3]dioxol-5-ylsulfonyl)-9-(2-bromo-ethyl)-9H-purin-6-ylamineand8-(6-bromo-benzo[1,3]dioxol-5-ylsulfonyl)-3-(2-bromo-ethyl)-3H-purin-6-ylamine(112 mg, 43%) were obtained as an inseparable 2:1 mixture of N9 and N3isomers according to the procedure described for examples 485 and 486step 1, using8-(6-bromo-benzo[1,3]dioxol-5-ylsulfonyl)-9H-purin-6-ylamine (200 mg,0.546 mmol). ¹H NMR (DMSO) δ 8.17 (s, 1H), 7.48 (brs, 2H), 7.36 (s, 1H),6.87 (s, 1H), 6.09 (s, 2H), 4.61 (t, J=6.0 Hz, 2H), 3.89 (t, J=6.0 Hz,2H; TOF LC-MS [M+H]⁺ 473.9

Step 2: Coupling of Step 1 product with 1-isopropyl piperazine

A mixture above Step 1 product (50 mg, 0.11 mmol) and 1-isopropylpiperazine (378 mg, 2.64 mmol) was heated at 55° C. for 10 h andpurified by preparative HPLC to afford the N9-isomer (8 mg) andN3-isomer (17 mg).8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(4-isopropylpiperazin-1-yl)ethyl]-9H-purin-6-amine.¹H NMR (CD₃OD) δ 8.32 (s, 1H), 7.27 (s, 1H), 7.22 (s, 1H), 6.09 (s, 2H),4.48 (t, J=5.6 Hz, 2H), 3.51-3.40 (m, 3H), 3.24-3.18 (m, 2H), 3.41-2.98(br t, J=10.8 Hz, 2H), 2.91 (t, J=5.6 Hz, 2H), 2.58-2.49 (m, 2H), 1.32(d, J=6.4 Hz, 6H); TOF-MS [M+H]⁺ 520.1.8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(4-isopropylpiperazin-1-yl)ethyl]-3H-purin-6-amine.¹H NMR (CD₃OD) δ 8.51 (s, 1H), 7.39 (s, 1H), 7.36 (s, 1H), 6.16 (s, 2H),4.51 (t, J=5.6 Hz, 2H), 3.48 (septet, J=6.4 Hz, 1H), 3.45-3.40 (m, 2H),3.19-3.14 (m, 2H), 3.00 (br d, J=10.0 Hz, 2H), 2.95 (t, J=5.6 Hz, 2H),2.49 (br t, J=11.2 Hz, 2H), 1.35 (d, J=6.4 Hz, 6H); TOF LC-MS [M+H]⁺520.1

Examples 489-495 were synthesized analogously to the procedure describedfor examples 487 and 488 using appropriate starting materials and wereisolated as a trifluoroacetate salts after preparative HPLCpurification. Their analytical data is summarized in table 9. TABLE 9Name and Analytical Example No. Structure Data 489

8-[(2,5-Dimethoxyphenyl)thio]-9-(2-piperidin-1-ylethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.34(s, 1H), 7.11(d, J=2.4 Hz, 1H), 7.05(d,J=8.8 Hz, 1H), 7.02(dd, J=8.8, 2.4 Hz, 1H),4.78(t, J=6.0 Hz, 2H), 3.85-3.78(m, 2H), 3.75(2s, 6H), 3.63(t, J=6.0 Hz,2H), 3.11-2.99(m, 2H), 2.05-1.72(m, 5H), 1.55(m, 1H); TOF LC-MS [M + H]⁺415.2 490

8-[(2,5-Dimethoxyphenyl)thio]-3-(2- piperidin-1-ylethyl)-3H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.51(s, 1H), 7.27(t, J=1.2 Hz, 1H), 7.17(d,J==1.2 Hz, 2H), 4.82(t, J=5.6 Hz, 2H), 3.80(s, 3H), 3.798(s, 3H),3.70(t, J=5.6 Hz, 2H), 3.15-2.88(m, 4H), 2.01-1.60(m, 6H); TOF LC-MS[M + H]^(+415.2) 491

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-piperidin-1-ylethyl)-9H-purin-6-amine NMR(CD₃OD) δ 8.33(s, 1H), 7.27 (s, 1H), 7.22(s, 1H),6.09(s, 2H), 4.75 (t, J=6.4 Hz, 2H), 3.88-3.78(m, 2H), 3.65(t, J=6.4 Hz,2H), 3.12-3.00(m, 2H), 2.40-1.72(m, 5H), 1.58(m, 1H); TOF-MS [M + H]⁺477.1 492

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-piperidin-1-ylethyl)-3H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.47(s, 1H), 7.35 (s, 1H), 7.30(s, 1H),6.13(s, 2H), 4.81 (t, J=6.0 Hz, 2H), 3.80-3.65(m, 2H), 3.68(t, J=6.0 Hz,2H), 3.14-2.94(m, 2H), 2.10-1.51(m, 6H); TOF LC-MS [M + H]⁺ 477.1 493

8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(4-isopropylpiperazin-1-yl)ethyl]-9H- purin-6-amine. ¹H NMR(CD₃OD)δ8.29(s, 1H), 7.04(dt, J=10.0 Hz, 2.0 Hz, 1H), 7.00(s, 1H), 6.99(dd,J=10.0, 2.4 Hz, 1H), 4.48(t, J=5.2 Hz, 2H), 3.75(s, 3H), 3.73(s, 3H),3.55 (s, 1H), 3.48-3.42(m, 2H), 3.20-3.13 (m, 2H), 2.95(br t, J=11.6 Hz,2H), 2.48(br t, J=11.6 Hz, 2H), 1.31(d, J=6.4 Hz, 6H); TOF LC-MS [M +H]⁺ # 458.2 494

9-[2-(4-Cyclopentylpiperazin-1- yl)ethyl]-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ 8.29(s, 1H),7.03(dt, J=10.0, 1.6 Hz, 1H), 7.01(s, 1H), 7.00(dd, J=10.0, 3.2 Hz, 1H),4.49(t, J=5.2 Hz, 2H), 3.75 (2s, 6H), 3.55-3.50(m, 2H), 3.47(m, 1H),3.19-3.14(m, 2H), 2.97-2.93(m, 2H), 2.88(t, J=5.2 Hz, 2H), 2.44(br t,J=12.8 Hz, 2H), 2.18-2.10(m, 2H), 1.88-1.78(m, 2H), 1.72- # 1.60(m, 4H);TOF LC-MS [M + H]⁺ 484.3 495

3-[2-(4-Cyclopentylpiperazin-1- yl)ethyl]-8-[(2,5-dimethoxyphenyl)thio]-3H-purin-6- amine. ¹H NMR(CD₃OD) δ 8.52(s, 1H),7.22-7.10(m, 2H), 4.52(t, J=5.6 Hz, 2H), 3.80(2s, 6H), 3.58-3.44(m, 3H),3.18-3.10(m, 2H), 3.10-2.96(m, 2H), 2.94(t, J=5.6 Hz, 2H), 2.57-2.44 (m,2H), 2.19-2.08(m, 2H), 1.88-1.78 (m, 2H), 1.72-1.64(m, 4H); TOF LC- MS[M + H]⁺ 484.2

Examples 496 and 497 Synthesis of1-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-2,6-dioneand1-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-2,6-dione

Title examples were prepared from Step 1 products of example 487 and 488using glutamide according to the procedure described for examples 485and 4861-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-2,6-dione¹H NMR (CD₃OD) δ 8.30 (s, 1H), 7.26 (s, 1H), 7.23 (s, 1H), 6.08 (s, 2H),4.53-4.49 (m, 2H), 4.26-4.23 (m, 2H), 2.55 (t, J=6.8 Hz, 4H), 1.86(quintet, J=6.8 Hz, 2H); TOF LC-MS [M+H]⁺ 505.0.1-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-2,6-dione.TOF LC-MS [M+H]⁺ 505.0.

Along with the desired products corresponding elimination products werealso isolated.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-vinyl-9H-6-ylamine (Example498) ¹H NMR (CD₃OD) δ 8.26 (s, 1H), 7.27 (s, 1H), 7.21 (dd, J=15.6, 9.6Hz, 1H), 7.16 (s, 1H), 6.27 (dd, J=15.6, 1.2 Hz, 1H), 6.09 (s, 2H), 5.47(dd, J=9.6, 1.2 Hz, 1H); LC-MS [M+H]⁺ 392.0.8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-vinyl-3H-6-ylamine (Example499). ¹H NMR (CD₃OD) δ 8.68 (s, 1H), 7.363 (s, 1H), 7.362 (dd, J=15.6,9.2 Hz, 1H), 7.35 (s, 1H), 6.27 (dd, J=15.6, 2.0 Hz, 1H), 6.15 (s, 2H),5.51 (dd, J=9.2, 2.0 Hz, 1H); LC-MS [M+H]⁺ 392.1

Examples 500-645 were prepared according to the procedure described forexamples 337 and 338 and isolated as a trifluoroacetate salts afterpreparative HPLC purification and summarized in table 10 TABLE 10Example Structure Name and analytical data 500

Methyl 4-({[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]carbonyl}amino)butanoate.¹H NMR (DMSO-d₆) δ 8.26(s, 1H), 7.40(s, 1H),6.88(s, 1H), 6.45-6.40(m, 1H), 6.10(s, 2H), 4.20(t, J=7.8 Hz, 2H),3.87(d, J=14.0 Hz, 2H), 3.57(s, 3H), 2.99(q, J=6.2 Hz, 2H), 2.60-2.40(m,2H), 2.27(t, J=7.4 Hz, 2H), 1.70-1.55(m, 6H), 1.40-1.25(m, 1H),1.05-0.90(m, 2H); # TOF-MS [M + H]⁺ 620.12 501

Methyl 4-({[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}ethyl)piperidin-1-yl]carbonyl}amino)butanoate. TOF-MS [M + H]^(+620.12) 502

4-({[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1- yl]carbonyl}amino)butanoic acid. ¹H NMR (DMSO-D₆)δ 12.03(s, 1H), 8.16(s, 1H), 7.55-7.42(broad s, 2H), 7.39(s, 1H), 6.8(s,1H), 6.45-6.40(m, 1H), 6.09(s, 2H), 4.17(t, J=7.8 Hz, 2H), 3.88(d,J=13.2 Hz, 2H), 2.99(q, J=5.8 Hz, 2H), 2.60-2.40(m, 2H), 2.18(t, J=7.4Hz, 2H), 1.65-1.55(m, 6H), 1.40- # 1.20(m, 1H), 1.00-0.90 (m, 2H);TOF-MS [M + H]⁺ 606.10 503

Methyl 4-({[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]carbonyl}amino)butanoate. ¹H NMR (CD₃OD) δ 8.25(s, 1H), 7.26(s, 1H),7.17(s, 1H), 6.08(s, 2H), 4.35(t, J=7.4 Hz, 2H), 3.95-3.75(m, 2H),3.68(s, 3H), 3.50-3.10(m, 2H), 2.90-2.80 (m, 1H), 2.63(dd, J=13.6, 10.5Hz, 1H), 2.37(t, J=7.4 Hz, 2H), 2.04-1.92(m, 1H), 1.88-1.66(m, 5H),1.56-1.36(m, # 2H), 1.30-1.20 (m, 1H); TOF-MS [M + H]⁺ 620.12 504

Methyl 4-({[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}ethyl)piperidin-1-yl]carbonyl}amino)butanoate. TOF-MS [M + H]⁺ 620.12 505

Methyl N-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]carbonyl}-L-methioninate. ¹H NMR(DMSO-D₆) δ 8.30(s, 1H), 7.38(s, 1H), 6.90(s, 1H),6.65(d, J=7.8 Hz, 1H), 6.08 (s,2H), 4.26-4.10(m, 4H), 3.95-3.85(m, 3H),3.57(s, 3H), 2.60-2.38(m, 2H), 2.00(s, 3H), 1.86(q, J=7.8 Hz, 2H),1.66-1.55(m, 4H), 1.40-1.28(m, 1H), 1.02-0.88(m, 2H); TOF-MS # [M + H]⁺666.10 506

Methyl N-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}ethyl)piperidin-1-yl]carbonyl}-L-methioninate. LC-MS [M + H]⁺ 666.1 507

Methyl N-{[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]carbonyl}-L-methioninate.¹H NMR(DMSO-D₆) δ 8.30(s, 1H), 7.40(s, 1H), 6.95(s, 1H),6.74-6.65(m, 1H), 6.11(s, 2H), 4.30-4.10(m, 3H), 3.88-3.70 (m, 2H),3.59(s, 3H), 2.80-2.60(m, 1H), 2.62-2.40(m, 1H), 2.30-2.20(m, 1H),2.02(s, 3H), 95-1.80(m, 3H), 1.73-1.50(m, 3H), 1.40-1.05 (m, 4H); #TOF-MS [M + H]⁺ 666.12 508

Methyl N-{[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}ethyl)piperidin-1-yl]carbonyl}-L-methioninate. LC-MS [M + H]⁺ 666.1 509

N-{[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}glycine. LC- MS [M + H]⁺ 578.0 510

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(cyclopentylcarbonyl)piperidin-4-yl]ethyl}- 9H-purin-6-amine. ¹HNMR(DMSO-D₆) δ 8.16 (s, 1H), 7.49(s, 1H), 7.05(s, 1H), 6.06(s, 2H),4.5(d, J=13.2 Hz, 1H), 4.29(t, J=7.2 Hz, 2H), 4.07(d, J=14.0 Hz, 1H),3.07-2.98(m, 2H), 2.57(dd, J=12.89, 3.1Hz, 1H), 1.92-1.50 (m, 9H), 1.38-1.25(m, 4H), 1.22-1.00(m, 2H); TOF-MS [M + H]⁺ 573.11 511

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(cyclopentylcarbonyl)piperidin-4-yl]ethyl }- 3H-purin-6-amine. LC-MS[M + H]⁺ 573.2 512

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(cyclobutylcarbonyl)piperidin-4-yl]ethyl}- 9H-purin-6-amine. ¹HNMR(CDCl₃) δ 8.19(s, 1H), 7.16(s, 1H), 7.09(s, 1H), 6.08(s, 2H), 4.62(d,J=13.6 Hz, 1H), 4.29(t, J=8.2 Hz, 2H), 3.72(d, J=14.8 Hz, 1H),3.60-3.40(m, 1H), 2.9(t, J=12.5 Hz, 1H), 2.52(t, J=12.5 Hz, 1H),2.40-2.28(m, 2H), 2.18-2.14(m, 2H), 1.9-2.0(m, 1H), 1.9-1.75(m, 5H),1.6-1.5(m, # 1H), 1.1-1.28(m, 2H); TOF-MS [M + H]⁺ 559.11 513

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(cyclobutylcarbonyl)piperidin-4-yl]ethyl}- 3H-purin-6-amine. TOF-MS[M + H]⁺ 559.11 514

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(cyclopropylcarbonyl)piperidin-4-yl]ethyl}- 9H-purin-6-amine. HNMR(CDCl₃) δ 8.32(s, 1H), 7.09(s, 1H), 6.84(s, 1H), 6.00(s, 2H),6.00-5.85 (broad s, 2H), 4.58(d, J=13.6 Hz, 1H), 4.27(t, J=7.4 Hz, 2H),4.21(d, J=13.6 Hz, 1H), 3.03(t, J=12.1Hz, 1H), 2.53(t, J=10.5 Hz, 1H),1.93 -1.70(m, SH), 1.60-1.48(m, 1H), 1.30-1.10(m, 2H), 0.99 -0.96(m,2H), 0.73 # (dd, J=8.2, 2.7 Hz, 2H); TOF-MS [M + H]^(+545.09) 515

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(cyclopropylcarbonyl)piperidin-4-yl]ethyl}- 3H-purin-6-amine. TOF-MS[M + H]⁺ 545.09 516

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}ethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.32(s, 1H), 7.28(s, 1H),7.21(s, 1H), 6.09 (s, 2H), 4.45-4.34(m, 4H), 3.00-2.50(broad hump, 2H),1.95-1.85(m, 4H), 1.68-1.56(m, 1H), 1.28(s, 3H), 1.26-1.10(m, 2H),0.90-0.84 (m, 2H), 0.64-0.60(m, 2H); TOF-MS [M + H]^(+559.01) 517

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}ethyl)-3H-purin-6-amine. LC-MS [M + H]^(+559.01) 518

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}ethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.26(s, 1H), 7.27(s, 1H),7.16(s, 1H), 6.08 (s, 2H), 4.5-4.4(m, 1H), 4.35(t, J=7.0 Hz, 2H),4.33-4.25(m, 1H), 3.15-3.03(m, 1H), 2.65-2.55(m, 1H), 2.00-1.75(m, 4H),1.70-1.58 (m, 2H), 1.30-1.19(m, 2H), 1.18-1.02(m, 5H), 0.66-0.58(m, 1H);TOF-MS [M + # H]⁺ 559.10 519

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}ethyl)-3H-purin-6-amine. LC-MS [M + H]^(+559.1) 520

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2- {1-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]piperidin-4- yl}ethyl)-9H-purin-6-amine.¹H NMR(CD₃OD) δ 8.19(s, 1H), 7.25(s, 1H), 7.08(s, 1H), 6.07 (s, 2H),4.45(d, J=13.6 Hz, 1H), 4.31(t, J=7.8 Hz, 2H), 4.04(d, J=13.6 Hz, 1H),3.03(t, J=12.1Hz, 1H), 2.56(t, J=12.8 Hz, 1H), 1.96-1.70(m, 5H),1.68-1.50(m, 1H), 1.25-1.00(m, 14H); TOF-MS # [M + H]⁺ 601.14 521

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2- {1-[(2,2,3,3-tetramethylcyc lopropyl)c arbonyl]piperidin-4-yl}ethyl)-3H-purin-6-amine. LC-MS [M + H]^(+601.1) 522

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-{[(2S)-2-fluorocyclopropyl]carbonyl}piperidin-4-yl)ethyl]-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.25(s, 1H), 7.9(s, 2H),7.27(s, 1H), 7.15(s, 1H), 6.08(s, 2H), 4.44(d, J=12.5 Hz, 1H), 4.35(t,J=8.2 Hz, 2H), 4.28(d, J=12.15 Hz, 1H), 3.20-3.05(m, 1H), 2.65-2.40(m,2H), 2.00-1.75(m, 4H), 1.70-1.55(m, 1H), 1.50-1.20(m, SH); TOF-MS [M+ #H]⁺ 563.07 523

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1-{[(2S)-2-fluorocyclopropyl]carbonyl}piperidin-4-yl)ethyl]-3H-purin-6-amine. LC-MS [M + H]^(+563.1) 524

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2- {1-[(2,2-difluorocyclopropyl)carbonyl]piperidin-4- yl}ethyl)-9H-purin-6-amine.¹HNMR(CDCl₃) δ 8.28(s, 1H), 7.1(s, 1H), 6.90(s, 1H), 6.00(s, 2H), 4.57(dd,J=25.7, 13.2 Hz, 1H), 4.27(t, J=7.4 Hz, 2H), 4.03(d, J=13.2 Hz, 1H),3.08(t, J=12.5 Hz, 1H), 2.70-2.47(m, 2H), 2.18-2.08 (m, 1H),2.00-1.48(m, 6H), 1.30-1.10(m, 2H); TOF-MS [M + H]⁺ # 581.08 525

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-(2- {1-[(2,2-difluorocyclopropyl)carbonyl]piperidin-4- yl}ethyl)-3H-purin-6-amine.¹HNMR(CDCl₃) δ 10.59(s, 1H), 8.06(s, 1H), 7.21(s, 1H), 7.17 (s, 1H),6.09(s, 2H), 4.56(dd, J=33.5, 15.2 Hz, 1H), 4.40-4.30(m, 2H), 4.04(d,J=14.4 Hz, 1H), 3.16-3.05(m, 1H), 2.74-2.48(m, 3H), 2.20-2.08(m, 1H),1.98-1.48(m, 4H), 1.30-1.10 (m, 3H); TOF-MS [M + H]⁺ # 581.08 526

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1- {[1-(trifluoromethyl)cyclopropyl]carbonyl}piperidin-4-yl)ethyl]-9H-purin-6-amine.¹H NMR (CDCl₃) δ 8.3(s, 1H), 7.08(s, 1H),6.86(s, 1H), 5.99(s, 2H), 4.65-4.27(m, 4H), 2.50-3.10 (2 broad peaks,2H), 1.86(d, J=13.6 Hz, 2H), 1.74(q, J=7.0 Hz, 2H), 1.57-1.48(m, 1H),1.20-1.35(m, 4H), 1.20-1.10(m, 2H); TOF-MS [M + H]⁺ 613.07 527

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1-(trifluoromethyl)cyclopropyl]carbonyl}piperidin-4-yl)ethyl]-3H-purin-6-amine. ¹H NMR (CDCl₃) δ 8.06(s, 1H), 7.21(s, 1H),7.17(s, 1H), 6.10(s, 2H), 4.70-4.20(m, 4H), 2.5-3.1(2 broad peaks, 2H),1.9(q, J=7.0 Hz, 1H), 1.82 (d, J=11.3 Hz, 1H), 1.48-1.58(m, 1H),1.12-1.38(m, 6H); TOF-MS [M + H]⁺ 613.07 528

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-(2,3-dihydro-1-benzofuran-5-ylthio)-9H-purin-6- amine. ¹H NMR(CD₃OD) δ8.28(d, J=3.1Hz, 1H), 7.49(s, 1H), 7.40(dd, J=3.1, 8.2 Hz, 1H), 6.84(d,J=8.2 Hz, 1H), 4.62(t, J=8.9 Hz, 2H), 4.50(d, J=13.2 Hz, 1H), 4.34(t,J=7.0 Hz, 2H), 3.91(d, J=13.6 Hz, 1H), 3.25(t, J=8.9 Hz, 2H), 3.07(t,J=12.5 Hz, 1H), 2.59(t, J=10.5 Hz, 1H), 2.08(s, 3H), 1.93-1.70(m, 4H), #1.68-1.50(m, 1H), 1.30-1.08(m, 2H); TOF-MS [M + H]⁺ 439.19 529

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-(2,3-dihydro-1-benzofuran-5-ylthio)-3H-purin-6- amine. LC-MS [M + H]⁺ 439.2530

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(7-bromo-2,3-dihydro-1-benzofuran-5-yl)thio]-9H- purin-6-amine.¹HNMR(CDCl₃) δ 8.23(s, 1H), 7.54(s, 1H), 7.31(s, 1H), 4.72-4.60(m, 3H),4.25(t, J=7.8 Hz, 2H), 3.82(d, J=13.6 Hz, 1H), 3.33(t, J=8.5 Hz, 2H),3.02(t, J=12.5 Hz, 1H), 2.52(t, J=12.8 Hz, 1H), 2.09(s, 3H), 1.86(t,J=15.2 Hz, 2H), 1.76(q, J=7.4 Hz, 2H), 1.60-1.48(m, 1H), 1.30-1.15(m,2H); TOF-MS # [M + H]⁺ 517.09 531

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(7-bromo-2,3-dihydro-1-benzofuran-5-yl)thio]-3H- purin-6-amine. LC-MS [M +H]⁺ 517.2 532

4-(2-{6-Amino-8-[(4-methyl-2-oxo-2H- chromen-7-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (DMSO-d₆) δ 8.33(s, 1H),7.92(s, 1H), 7.76(d, J=8.0 Hz, 1H), 7.37(s, 1H), 7.28(d, J=8.0 Hz, 1H),6.42(s, 1H), 4.24(t, J=7.6 Hz, 2H), 4.10-4.00(m, 1H), 3.60-3.56(m, 1H),2.91-2.84 (m, 1H), 2.53-2.45(m, 2H), 2.40(s, 3H), 1.75-1.60(m, 3H),1.50-1.40(m, 1H), 1.00-0.85(m, 2H). TOF-MS [M + # H]⁺ 465.1 533

4-(2-{6-Amino-8-[(4-methyl-2-oxo-2H- chromen-7-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (DMSO-d₆) δ 8.59(s, 1H),7.93(s, 1H), 7.78(d, J=8.4 Hz, 1H), 7.64(s, 1H), 7.50(d, J=8.4 Hz, 1H),6.43(s, 1H), 4.34(t, J=8.0 Hz, 2H), 4.10-4.00(m, 1H), 3.65-3.56(m, 1H),2.96-2.84 (m, 1H), 2.53-2.45(m, 2H), 2.43(s, 3H), 1.86-1.71(m, 3H),1.55-1.45(m, 1H), 1.10-0.85(m, 2H). TOF-MS [M + # H]⁺ 465.1 534

4-(2-{6-Amino-8-[(5-methoxy-1,3-benzoxazol-7-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1- carbaldehyde. ¹HNMR(DMSO-d₆) δ 8.30(s, 1H), 8.26(s, 1H), 7.93(s, 1H), 7.55(s, 1H),6.42(s, 1H), 4.30-4.20(m, 2H), 4.15-4.05(m, 1H), 3.59(s, 3H),3.65-3.50(m, 1H), 2.95-2.85 (m, 1H), 2.50-2.45(m, 2H), 1.75-1.35(m, 4H),1.00-0.85(m, 2H). TOF-MS [M + H]⁺ 454.0 535

4-(2-{6-Amino-8-[(5-methoxy-1,3-benzoxazol-7-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1- carbaldehyde.¹HNMR(DMSO-d₆) δ 8.35(s, 1H), 8.12(s, 1H), 7.96(s, 1H), 7.87(s, 1H),6.88(s, 1H), 4.33(t, J=7.2 Hz, 2H), 4.15-4.10 (m, 1H), 3.69(s, 3H),3.65-3.61(m, 1H), 2.99-2.92(m, 1H), 2.50-2.45(m, 2H), 1.85-1.71(m, 3H),1.60-1.45(m, 1H), 1.10-0.9(m, 2H). TOF- MS [M + H]⁺ 454.0 536

4-(2-{6-Amino-8-[(2-methoxy-5- nitrophenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (CD₃OD) δ 8.36(d, J=8.8 Hz,1H), 8.33(s, 1H), 8.29(s, 1H), 7.97(s, 1H), 7.31(d, J=8.8 Hz, 1H),4.41(t, J=7.6 Hz, 2H), 3.96(s, 3H), 3.74-3.68(m, 1H), 3.13-3.04(m, 2H),2.67-2.60 (m, 2H),1.93-1.80(m, 3H), 1.70-1.55(m, 1H), 1.22-1.09(m, 2H).TOF-MS [M + H]⁺ 458.0 537

4-(2-{6-Amino-8-[(2-methoxy-5- nitrophenyl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (CD₃OD) δ 8.40-8.38(m, 2H),8.29(d, J=9.2 Hz, 1H), 7.97(s, 1H), 7.27(d, J=9.2 Hz, 1H), 4.40(t, J=7.6Hz, 2H), 3.99(s, 3H), 2.96-2.84 (m, 2H), 1.93-1.00(m, 5H). TOF-MS [M +H]^(+458.0) 538

4-(2-{6-Amino-8-[(4-methoxypyridin-2-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR(CD₃OD) δ 8.25(s,1H), 8.20(d, J=5.2 Hz, 1H), 7.95(s, 1H), 6.97(s, 1H), 6.88(d, J=5.2 Hz,1H), 4.35(t, J=7.6 Hz, 2H), 3.85 (s, 3H), 3.06-2.99(m, 1H), 2.60-2.55(m,1H), 1.89-0.80(m, SH). TOF-MS [M + H]⁺ 414.1 539

4-{2-[6-Amino-8-(1-benzofuran-5-ylthio)-9H-purin-9-yl]ethyl}piperidine-1-carbaldehyde. ¹H NMR(CD₃OD) δ 8.28(s, 1H),8.00-7.95(m, 2H), 7.89-7.87(m, 1H), 7.65-7.60(m, 1H), 7.60-7.54(m, 1H),6.96(s, 1H), 4.45-4.30(m, 3H), 3.25-3.00(m, 1H), 2.70-2.60(m, 1H),1.95-1.55(m, SH), 1.00-0.85(m,1H). LC-MS [M + H]⁺ 423.1 540

4-(2-{6-Amino-8-[(3,4,5- trimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde.. LC-MS [M + H]⁺ 473.2 541

4-(2-{6-Amino-8-[(3,4,5- trimethoxyphenyl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (DMSO-d₆) δ 8.64(s, 1H),7.96(s, 1H), 7.06(s, 2H), 4.35(t, J=7.2 Hz, 2H), 4.15-4.10(m, 1H),3.79(s, 6H), 3.71(s, 3H), 3.65-3.62(m, 1H), 2.99-2.90(m, 2H),2.60-2.45(m, 2H), 1.83-1.71 (m, 2H), 1.03-0.80(m, 3H). LC-MS [M +H]^(+473.2) 542

Methyl 2-({6-amino-9-[2-(1-formylpiperidin-4-yl)ethyl]-9H-purin-8-yl}thio)isonicotinate. ¹H NMR(DMSO-d₆) δ 8.61(d,J=5.2 Hz, 1H), 8.28(s, 1H), 7.91(s, 1H), 7.70(s, 1H), 7.68(d, J=5.2 Hz,1H), 4.22(t, J=7.6 Hz, 2H), 4.07-4.03(m, 1H), 3.86(s, 3H), 3.59-3.56(m,1H), 2.90-2.82(m, 1H), 2.50-2.45(m, 2H), 1.70-1.60 (m, 3H), 1.48-1.35(m,1H), 0.97-0.83(m, 2H). LC-MS [M + H]⁺ 442.2 543

Methyl 2-({6-amino-3-[2-(1-formylpiperidin-4-yl)ethyl]-3H-purin-8-yl}thio)isonicotinate. ¹H NMR(DMSOd₆) δ 8.69(d,J=4.8 Hz, 1H), 8.58(s, 1H), 8.09(s, 1H), 7.95(s, 1H), 7.69(d, J=4.8 Hz,1H), 4.36(t, J=7.2 Hz, 2H), 4.15-4.05(m, 1H), 3.85(s, 3H), 3.65-3.60(m,1H), 2.99-2.90(m, 1H), 2.50-2.45(m, 2H), 1.90-1.7 (m, 3H), 1.60-1.50(m,1H), 1.10-0.90(m, 2H). LC-MS [M + H]⁺ 442.2 544

4-(2-{6-Amino-8-[(6-methoxypyrimidin-4-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1- carbaldehyde. ¹H NMR(CD₃OD) δ8.50(s, 1H), 8.33(s, 1H), 7.95(s, 1H), 6.79(s, 1H), 4.35(t, J=7.2 Hz,2H), 4.27-4.23(m, 1H), 3.96(s, 3H), 3.68-3.65(m, 1H), 3.06-2.99(m, 2H),2.65-2.55 (m, 1H), 1.86-1.75(m, 4H), 1.15-1.01(m, 2H). LC-MS [M + H]⁺415.2 545

4-(2-{6-Amino-8-[(7-bromo-2,3-dihydro-1,4-benzodioxin-6-yl)thio]-9H-purin-9- yl}ethyl)piperidine-1-carbaldehyde.¹H NMR (DMSO-d₆) δ 8.17(s, 1H), 7.93(s, 1H), 7.28(s, 1H), 6.96(s, 1H),4.25-4.05(m, 3H), 3.65-3.55 (m, 1H), 2.95-2.85(m, 1H), 2.50-2.45(m, 4H),1.75-1.35(m, 6H), 1.00-0.85(m, 2H).LC-MS [M + H]⁺ 519.1 546

4-(2-{6-Amino-8-[(3-methyl-2-thienyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR(DMSO-d₆) δ 8.28(s,1H), 7.96(s, 1H), 7.74(d, J=5.2 Hz, 1H), 7.10(d, J=5.2 Hz, 1H), 4.25(t,J=8.00 Hz, 2H), 4.14-4.10(m, 2H), 3.16(s, 3H), 3.00-2.90(m, 2H),1.60-0.80 (m, 7H). LC-MS [M + H]⁺ 403.2 547

4-(2-{6-Amino-8-[(3-methyl-2-thienyl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR(DMSO-d₆) δ 8.65(s,1H), 7.97(s, 1H), 7.91(d, J=5.6, 1H), 7.23(d, J=5.6 Hz, 1H), 4.32(t,J=7.6 Hz, 2H), 4.13-4.09(m, 2H), 2.98-2.9 1(m, 1H), 2.57-2.50(m, 2H),2.30(s, 3H), 1.60-0.80(m, 6H). LC-MS [M + H]⁺ 403.1 548

N-[4-({6-Amino-9-[2-(1-formylpiperidin-4-yl)ethyl]-9H-purin-8-yl}thio)-3- chlorophenyl]acetamide. ¹H NMR(DMSO-d₆)δ8.21(s, 1H), 7.98(s, 1H), 7.93(s, 1H), 7.39(d, J=8.4 Hz, 1H), 7.21(d,J=8.4 Hz, 1H), 4.19 (t, J=7.2 Hz, 2 H), 4.12-4.06(m, 1H), 3.70-3.50(m,3H), 2.92-2.86(m, 1H), 2.50-2.45(m, 2H), 2.05(s, 3H), 1.70-0.80(m, 4H).LC-MS [M + H]⁺ 474.2 549

N-[4-({6-Amino-3-[2-(1-formylpiperidin-4-yl)ethyl]-3H-purin-8-yl}thio)-3- chlorophenyl]acetamide.. ¹HNMR(DMSO-d₆) δ8.60(s, 1H), 8.04(s, 1H), 7.95(s, 1H), 7.70-7.60(m, 1H),7.55-7.48(m, 1H), 4.29(t, J=8.0 Hz, 2 H), 4.15-4.05(m, 1H), 3.70-3.50(m,2H), 2.97-2.90(m, 3H), 2.50-2.45(m, 2H), 2.09(s, 3H), 1.70-0.80(m, 3H).LC-MS [M + H]⁺ 474.1 550

4-(2-{6-Amino-8-[(3-bromopyridin-2-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. NMR(CD₃OD) δ 8.41(s, 1H),8.22(dd, J=4.8, 1.6 Hz, 1H), 8.04(dd, J=8.0, 1.6 Hz, 1H), 7.95(s, 1H),7.17(q, J=8.0, 4.8 Hz, 1H), 4.33 (t, J=8.4 Hz, 2H), 4.27-4.22(m, 1H),3.70-3.64 (m, 1H), 3.06-2.99(m, 2H), 2.66-2.55(m, 1H), 1.85-1.77(m, 2H),1.65-1.55(m, 1H), 1.13-1.00 (m, 3H). TOF-MS [M + H]⁺ 463.9 551

4-(2-{6-Amino-8-[(3-bromopyridin-2-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR(CD₃OD) δ 8.64(s,1H), 8.61(dd, J=4.8, 1.6 Hz, 1H), 8.17(dd, J=8.0, 1.6 Hz, 1H), 7.99(s,1H), 7.36(q, J=8.0, 4.8 Hz, 1H), 4.51 (t, J=8.0 Hz, 2H), 4.33-4.25(m,1H), 3.75-3.70 (m, 1H), 3.15-3.08(m, 2H), 2.75-2.64(m, 1H), 1.98-1.85(m,2H), 1.75-1.65(m, 1H), 1.30-1.10 (m, 3H). TOF-MS [M + H]⁺ # 463.9 552

4-(2-{6-Amino-8-[(3-bromopyridin-2-yl)thio]-7H-purin-7-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR(CD₃OD) δ 8.46(s,1H), 8.27(dd, J=4.8, 1.6 Hz, 1H), 8.06(dd, J=8.0, 1.6 Hz, 1H), 7.94(s,1H), 7.20(q, J=8.0, 4.8 Hz, 1H), 4.55 (t, J=8.0 Hz, 2H), 4.25-4.15(m,1H), 3.70-3.60 (m, 1H), 3.15-3.08(m, 2H), 2.65-2.55(m, 1H), 1.80-1.60(m,3H), 1.10-0.90(m, 3H). TOF-MS [M + H]⁺ 463.9 553

4-[2-(6-Amino-8-{[4,5-bis(benzyloxy)-2- bromophenyl]thio}-9H-purin-9-yl)ethyl]piperidine-1-carbaldehyde. ¹H NMR (CD₃OD) δ 8.21(s, 1H),7.94(s, 1H), 7.47-7.30 (m, 6H), 7.12-7.01(m, SH), 6.86(s, 1H), 5.15 (s,2H), 5.07(s, 2H), 4.25-4.18(m, 1H), 4.11(t, J=7.6 Hz, 2H), 3.65-3.58(m,2H), 2.99-2.91 (m, 1H), 2.57-2.49(m, 1H), 1.74-1.64(m, 2H), 1.43-1.35(m,1H), 1.10-0.89(m, 3H); TOF-MS [M + # H]⁺ 673.1 554

4-[2-(6-Amino-8-{[4,5-bis(benzyloxy)-2- bromophenyl]thio}-3H-purin-3-yl)ethyl]piperidine-1-carbaldehyde. ¹H NMR (CD₃OD) δ 8.26(s, 1H),7.95(s, 1H), 7.47-7.14 (m, 12H), 5.15(s, 2H), 5.05(s, 2H), 4.33(t, J=7.6Hz, 2H), 4.28-4.24(m, 1H), 3.68-3.63(m, 1H), 3.09-3.00(m, 2H),2.67-2.55(m, 1H), 1.88-1.78(m, 3H), 1.63-1.60(m, 1H), 1.20-1.00 (m, 2H).TOF-MS [M + H]⁺ 673.16 555

4-(2-{6-Amino-8-[(1-oxo-2,3-dihydro-1H-inden-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1- carbaldehyde.¹H NMR(CD₃OD)δ 8.29(s, 1H), 7.95(s, 1H), 7.70(d, J=8.4 Hz, 1H), 7.36(s, 1H), 7.45(d,J=8.4 Hz, 1H), 4.35(t, J=7.6 Hz, 2H), 4.28-4.24(m, 1H), 3.70-3.64(m,1H), 3.17-3.00(m, 6H), 2.75-2.57(m, 4H), 1.85-1.70 (m, 3H). TOF-MS [M +H]⁺ 437.18 556

4-(2-{6-Amino-8-[(4-methoxy-7-methyl-2,3-dihydro-1H-inden-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (CD₃OD) δ 8.28(s, 1H),7.98(s, 1H), 7.16(s, 4.36(t, J=7.6 Hz, 2H), 4.35-4.27(m, 1H), 3.73(s,3H), 3.72-3.68(m, 1H), 3.14-3.05(m, 2H), 3.01(t, J=8.0 Hz, 2H), 2.86(t,J=7.6 Hz, 2H), 2.70-2.64(m, 1H), 2.21(s, 3H), 2.15-2.10 (m, 2H),1.89-1.55(m, 3H), 1.20-1.05(m, 3H); TOF-MS # [M + H]⁺ 467.2 557

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.28(s, 1H),7.07-7.00(m, 3H), 4.50-4.44(m, 1H), 4.37(t, J=7.6 Hz, 2H), 3.94-3.85(m,1H), 3.74(s, 6H), 3.13-3.04(m, 2H), 2.60-2.52(m, 1H), 2.08(s, 3H),1.90-1.74 (m, 3H), 1.60-1.55(m, 1H), 1.24-1.06(m, 2H). TOF-MS [M + H]⁺457.2 558

4-(2-{6-Amino-8-[(4-chloro-2,5- dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR (CD₃OD) δ 8.31(s, 1H),7.98(s, 1H), 7.33(s, 1H), 7.22(s, 1H), 4.40(t, J=7.6 Hz, 2H),4.33-4.29(m, 1H), 3.84(s, 3H), 3.74(s, 3H), 3.74-3.68(m, 1H),3.14-3.06(m, 2H), 2.69-2.62(m, 1H), 1.95-1.58(m, 4H), 1.29-1.11(m, 2H).TOF-MS [M + H]⁺ 477.1 559

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2,5-difluoro-4-methoxyphenyl)thio]-9H-purin-6- amine.¹H NMR(CD₃OD) δ 8.28(s,1H), 7.51 (dd, J=10.4, 3.2 Hz, 1H), 7.17(dd, J=10.4, 3.2 Hz, 1H),4.53-4.48(m, 1H), 4.38(t, J=7.6 Hz, 2H), 3.93(s, 3H), 3.93-3.90(m, 1H),3.13-3.04(m, 2H), 2.62-2.57(m, 1H), 2.10-2.07(m, 1H), 2.08(s, 3H),1.95-1.55(m, 3H), 1.3 1-1.12 (m, 2H); TOF-MS [M + H]⁺ 463.1 560

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2-bromo-4,5-difluorophenyl)thio]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ8.32(s, 1H), 7.84 (dd, J=10.0, 3.6 Hz, 1H), 7.69(dd, J=10.0, 3.6 Hz,1H), 4.53-4.47(m, 1H), 4.39(t, J=7.6 Hz, 2H), 3.93-3.88(m, 1H),3.13-3.00(m, 2H), 2.65-2.52(m, 1H), 2.10-2.07(m, 1H), 2.08(s, 3H),1.90-1.56(m, 3H), 1.30-1.08(m, 2H). TOF-MS[M + H]⁺ 511.0 561

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-(1,3-benzodioxol-5-ylthio)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.28(s, 1H),7.19-7.11(m, 2H), 6.93(d, J=7.6 Hz, 1H), 6.04(s, 2H), 4.52-4.48(m, 1H),4.33(t, J=8.4 Hz, 2H), 3.95-3.86 (m, 1H), 3.13-3.04(m, 2H), 2.62-2.52(m,1H), 2.08(s, 3H), 1.95-1.50(m, 3H), 1.26-1.18(m, 3H). TOF-MS [M + H]⁺441.16 562

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-(1,3-benzodioxol-5-ylthio)-3H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.54(s, 1H),7.29(dd, J=8.4, 1.6 Hz,1H), 7.23(d, J=1.6 Hz, 1H), 7.03(d, J=8.4 Hz,1H), 6.11(s, 2H), 4.51-4.41(m, 1H), 4.13(t, J=7.2 Hz, 2H), 3.95-3.86(m,1H), 3.13-3.04(m, 2H), 2.64-2.55(m, 1H), 2.10-2.02 (m, 1H), 2.03(s, 3H),1.92-1.50(m, 3H), 1.20-1.10(m, 2H). TOF-MS [M + H]⁺ 441.16 563

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(4-cloro-2,5-dimethoxyphenyl)thio]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ8.29(s, 1H), 7.32 (s, 1H), 7.22(s, 1H), 4.52-4.47(m, 1H), 4.38(t, J=8.0Hz, 2H), 3.94-3.88(m, 1H), 3.84(s, 3H), 3.74(s, 3H), 3.14-3.02(m, 2H),2.69-2.55(m, 1H), 2.09(s, 3H), 1.9S-1.78(m, 2H), 1.60-1.55 (m, 2H),1.29-1.11(m, 2H). TOF-MS [M + H]^(+491.15) 564

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(2,2,2-trifluoroethyl)piperidin-2-yl]ethyl}- 9H-purin-6-amine. ¹HNMR(CD₃OD) δ 8.27(s, 1H), 7.19(s, 1H), 7.08(s, 1H), 6.04(s, 2H),4.40-4.28(m, 2H), 4.08-4.04(m, 1H), 3.72-3.60 (m, 1H), 3.18-3.10(m, 2H),2.96(s, 2H), 2.95-2.92(m, 1H), 2.6-2.52(m, 1H), 2.1-2.00(m, 1H),1.82-1.74(m, 1H), 1.68-1.50(m, 3H). TOF-MS [M + H]⁺ 557.98 565

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2-bromo-4,5-dimethoxyphenyl)thio]-9H-purin-6- ¹H NMR(CD₃OD) δ 8.32(s, 1H),7.35(s, 1H), 7.34(s, 1H), 4.52-4.47(m, 1H), 4.39(t, J=7.6 Hz, 2H),3.95-3.87(m, 1H), 3.88(s, 3H), 3.82(s, 3H), 3.12-3.03(m, 2H),2.63-2.55(m, 1H), 2.09(s, 3H), 1.94-1.50(m, 4H), 1.23-1.08 (m, 3H).TOF-MS [M + H]⁺ 535.1 566

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2-bromo-4,5-dimethoxyphenyl)thio]-3H-purin-6- amine. ¹H NMR(CD₃OD) δ8.53(s, 1H), 7.45 (s, 1H), 7.43(s, 1H), 4.52-4.47(m, 1H), 4.42(t, J=8.0Hz, 2H), 3.95-3.87(m, 1H), 3.92(s, 3H), 3.86(s, 3H), 3.12-3.03(m, 2H),2.64-2.56(m, 1H), 2.10(s, 3H), 1.94-1.50(m, 4H), 1.23-1.08 (m, 3H).TOF-MS [M + H]⁺ 535.1 567

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(3-fluoro-4-methoxyphenyl)thio]-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.19(s, 1H),7.43-7.37(m, 2H), 7.23-7.17(m, 1H), 4.52-4.44(m, 1H), 4.31 (t, J=8.0 Hz,2H), 3.95-3.87(m, 1H), 3.91(s, 3H), 3.14-3.00(m, 2H), 2.62-2.53(m, 1H),2.08 (s, 3H), 1.89-1.50(m, 4H), 1.23-1.08(m, 2H). TOF-MS [M + H]⁺ 445.17568

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(3-fluoro-4-methoxyphenyl)thio]-3H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.53(s, 1H),7.58-7.50(m, 2H), 7.32-7.28(m, 1H), 4.52-4.44(m, 1H), 4.41 (t, J=7.6 Hz,2H), 3.97(s, 3H), 3.93-3.86(m, 1H), 3.13-3.03(m, 2H), 2.64-2.54(m, 1H),2.09 (s, 3H), 1.89-1.50(m, 4H), 1.23-1.08(m, 2H). TOF-MS [M + H]⁺445.17. 569

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(3-chloro-5-fluoro-4-methoxyphenyl)thio]-9H- purin-6-amine.1 NMR(CD₃OD) δ8.26(s, 1H), 7.5 1-7.49(m, 1H), 7.46-7.42(m, 1H), 4.52-4.45 (m, 1H),4.34(t, J=7.6 Hz, 2H), 3.98(s, 3H), 3.94-3.87(m, 1H), 3.14-3.00(m, 2H),2.61-2.53 (m, 1H), 2.08(s, 3H), 1.89-1.50(m, 4H), 1.23-1.08(m, 2H).TOF-MS [M + H]⁺ 479.15 570

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(3-chloro-5-fluoro-4-methoxyphenyl)thio]-3H- purin-6-amine. ¹H NMR(CD₃OD) δ8.46(s, 4.5 1-4.46(m, 1H), 4.40(t, J=7.2 Hz, 2H), 4.02 (s, 3H),3.94-3.86(m, 1H), 3.16-3.02(m, 2H), 2.62-2.55(m, 1H), 2.09(s, 3H),1.89-1.50(m, 4H), 1.30-1.10(m, 2H). TOF-MS [M + H]^(+479.15) 571

9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2,2-difluoro-1,3-benzodioxol-5-yl)thio]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ8.33(s, 1H), 7.62 (d, J=1.6 Hz,1H), 7.50(dd, J=8.4, 1.6 Hz, 1H), 7.34(d,J=8.4 Hz, 1H), 4.52-4.75(m, 1H), 4.37(t, J=7.6 Hz, 2H), 3.93-3.88(m,1H), 3.11-3.02(m, 2H), 2.62-2.55(m, 1H), 2.10-2.06 (m, 1H), 2.08(s, 3H),1.92-1.50(m, 3H), 1.20-1.10(m, 2H). TOF-MS [M + H]⁺ # 477.15 572

3-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(2,2-difluoro-1,3-benzodioxol-5-yl)thio]-3H-purin-6- amine. ¹H NMR(CD₃OD) δ8.54(s, 1H), 7.70 (d, J=1.6 Hz,1H), 7.60(dd, J=8.4, 1.6 Hz, 1H), 7.42(d,J=8.4 Hz, 1H), 4.5 1-4.46(m, 1H), 4.41(t, J=7.6 Hz, 2H), 3.95-3.86(m,1H), 3.13-3.04(m, 2H), 2.64-2.55(m, 1H), 2.10-2.02 (m, 4H), 1.92-1.50(m,3H), 1.20-1.10(m, 2H). TOF-MS [M + H]⁺ 477.15 573

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(4-chlorobenzyl)piperidin-4-yl]ethyl}-9H- purin-6-amine. ¹HNMR(CD₃OD) δ 8.20(s, 1H), 7.55-7.47(m, 4H), 7.27(s, 1H), 7.12(s, 1H),6.08(s, 2H), 4.35-4.25(m, 3H), 3.10-2.80 (m, 2H), 2.15-1.8(m, 3H),2.05(s, 2H), 1.60-0.80(m, 5H). TOF-MS [M + H]⁺ 601.0 574

N-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)quino un-8-amine. ¹H NMR(CD₃OD) δ 8.63(dd,J=4.0, 1.6 Hz, 1H), 8.17(s, 1H), 8.11(d, J=8.4 Hz, 1H), 7.40 (dd, J=8.4,4.0 Hz, 1H), 7.27(t, J=8.0 Hz, 1H), 7.12(s, 1H), 7.04(d, J=8.4 Hz, 1H),6.83 (s, 1H), 6.69(d, 8.0 Hz, 1H), 5.99(s, 2H), 4.62 (t, J=5.6 Hz, 2H),3.92(t, J=5.6 Hz, 2H). TOF-MS [M + H]⁺ 536.0 575

1-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-4- carbonitrile. ¹H NMR(CD₃OD) δ8.35(s, 1H), 7.29(s, 1H), 7.27(s, 1H), 6.10(s, 2H), 4.46-4.41(m, 2H),2.96-2.90(m, 2H), 1.90-1.50(m, 9H). TOF-MS [M + H]⁺ 502.0 576

1-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-7H-purin-7-yl}ethyl)piperidine-4 - carbonitrile. ¹H NMR(CD₃OD)δ 8.49(s, 1H), 7.36(s, 1H), 7.34(s, 1H), 6.14(s, 2H), 4.78-4.70(m, 2H),3.62-3.58(m, 2H), 1.90-1.50(m, 9H). TOF-MS [M + H]⁺ 502.0 577

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(2,2,2-trifluoroethyl)piperidin-3-yl]ethyl}- 9H-purin-6-amine. ¹HNMR(CD₃OD) δ 8.27(s, 1H), 7.28(s, 1H), 7.18(s, 1H), 6.09(s, 2H), 4.37(t,J=7.2 Hz, 2H), 3.59-3.50(m, 2H), 2.84-2.76(m, 1H), 2.79(s, 2H),2.58-2.50(m, 1H), 1.94-1.50(m, 7H). TOF-MS [M − H]⁻ 557.04 578

3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-6- methylpyrimidine-2,4(1H,3H)-dione. ¹HNMR (CD₃OD) δ 8.26(s, 1H), 7.25(s, 1H), 7.15(s, 1H), 6.08(s, 2H),5.40(s, 1H), 4.65-4.60(m, 2H), 4.38-4.36(m, 2H), 2.07(s, 3H). LC-MS [M −H]⁺ 517.8 579

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(4-fluorobenzyl)piperidin-4-yl]ethyl}-9H- purin-6-amine. ¹HNMR(CD₃OD) δ 8.18(s, 1H), 7.55-7.50(m, 2H), 7.27-7.22(m, 3H), 7.09 (s,1H), 6.08(s, 2H), 4.31(t, J=7.2 Hz, 2H), 4.27(s, 2H), 3.50-3.47(m, 2H),2.99-2.91(m, 2H), 2.16-2.10(m, 2H), 1.90-1.40(m, 5H). TOF-MS [M + H]⁺585.1 580

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-(2-pyrrolidin-1-ylethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.30(s, 1H),7.27(s, 1H), 7.19 (s, 1H), 6.08(s, 2H), 4.70(t, J=6.4 Hz, 2H), 3.78(t,J=6.4 Hz, 2H), 3.50-3.47(m, 4H), 2.40-2.00(m, 4H). LC-MS [M + H]⁺ 463.3581

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(cyclohexylmethyl)piperidin-4-yl]ethyl}-9H- purin-6-amine. ¹HNMR(CD₃OD) δ 8.20(s, 1H), 7.27(s, 1H), 7.10(s, 1H), 6.08(s, 2H),4.35-4.30(m, 2H), 3.60-3.53(m, 2H), 2.93-2.84(m, 4H), 2.16-0.80 (m,18H). TOF-MS [M + H]⁺ 573.1 582

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-isopropylpiperidin-4-yl)ethyl]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ8.23(s, 1H), 7.27 (s, 1H), 7.13(s, 1H), 6.08(s, 2H), 4.38-4.30(m, 2H),3.62-3.52(m, 2H), 3.36-3.26(m, 1H) 3.05-2.98(m, 2H), 2.96-2.84(m, 2H),1.8-0.80(m, 11H). TOF-MS [M + H]⁺ 519.1 583

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-7-[2-(1-isopropylpiperidin-4-yl)ethyl]-7H-purin-6- amine.1 NMR(CD₃OD) δ 8.15(s,1H), 7.26(s, 1H), 7.2(s, 1H), 6.09(s, 2H), 3.50-3.47(m, 5H),1.80-0.80(m, 15H). TOF-MS [M + H]^(+519.1) 584

1-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)pyrrolidin-2-one. ¹H NMR(CDCl₃) δ 8.31(s,1H), 7.25(s, 1H), 7.23(s, 1H), 6.08(s, 2H), 4.5 1-4.46(m, 2H),3.78-3.74(m, 2H), 3.62-3.56(m, 2H), 2.20-2.15 (m, 2H), 2.10-2.05(m, 2H).TOF-MS [M + H]^(+477.0) 585

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]ethyl}- 9H-purin-6-amine. ¹HNMR(CD₃OD) δ 8.29(s, 1H), 7.28(s, 1H), 7.18(s, 1H), 6.09(s, 2H), 4.35(t,J=7.2 Hz, 2H), 3.56-3.50(m, 2H), 3.35 (s, 2H), 3.30-3.25(m, 2H),2.69-2.59(m, 3H), 2.00-1.40(m, 4H). TOF-MS [M + H]⁺ 559.0 586

3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-1,3-oxazolidin-2- one. ¹H NMR(CD₃OD) δ8.31(s, 1H), 7.27(s, 1H), 7.22(s, 1H), 6.08(s, 2H), 4.52(t, J=7.6 Hz,2H), 4.32(t, J=8.8 Hz, 2H), 3.81(t, J=8.8 Hz, 2H), 3.74(t, J=7.6 Hz,2H). TOF-MS [M + H]⁺ 479.0 587

3-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-1,3-oxazolidin-2- one. ¹H NMR(CD₃OD) δ8.55(s, 1H), 7.38(s, 1H), 7.37(s, 1H), 6.15(s, 2H), 4.58(t, J=9.2 Hz,2H), 4.32(t, J=7.6 Hz, 2H), 3.80-3.75(m, 4H). TOF-MS [M + H]⁺ 479.0 588

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(cyclohexylmethyl)piperidin-2-yl]ethyl}-9H- purin-6-amine. HNMR(Acetone d₆) δ 8.36(s, 1H), 7.27(s, 1H), 7.01(s, 1H), 6.13(s, 2H),4.50-4.48(m, 2H), 3.70-3.50(m, 5H), 3.30-3.20 (m, 2H), 2.10-0.80(m,17H). TOF-MS [M + H]^(+573.1) 589

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(cyclohexylmethyl)piperidin-2-yl]ethyl}-3H- purin-6-amine. TOF-MS[M + H]⁺ 573.1 590

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(4-methoxybenzyl)piperidin-2-yl]ethyl}-9H- purin-6-amine. ¹HNMR(CD₃OD) δ 8.30(s, 1H), 7.41-7.15(m, 4H), 6.98-6.84(m, 2H),6.10-6.03(m, 2H), 4.80-4.60(m, 2H), 3.85-3.78(m, 6H), 2.10-1.50 (m,10H). TOF-MS [M − H]⁺ 597.0 591

Benzyl 4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-5-oxo-1,3-oxazolidine-3-carboxylate. ¹H NMR (DMSO-d₆) δ 8.23(s, 1H),7.37-7.13(m, 7H), 6.64(s, 2H), 6.02(s, 2H), 5.38(s, 2H), 5.10-5.00(m,1H), 4.80-4.70(m, 2H), 3.60-3.30(m, 2H). TOF-MS [M + H]⁺ 613.0 592

Benzyl 2-(2-{6-amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate. ¹H NMR (DMSO-d₆) δ 8.29(s, 1H),7.36(s, 1H), 7.35-7.24(m, 5H), 6.85(s, 1H), 6.07(s, 2H), 5.00(s, 2H),4.25-3.87(m, 6H), 2.80-2.65(m, 1H), 2.20-1.75(m, 2H), 1.60-1.40(m, 4H).TOF-MS [M + H]⁺ 611.0 593

Benzyl 2-(2-{6-amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate. ¹H NMR (DMSO-d₆) δ 8.58(s, 1H),7.49(s, 1H), 7.41-7.14(m, 5H), 6.68(s, 1H), 6.15(s, 2H), 5.40(s, 2H),4.25-4.10(m, 4H), 3.70-3.60(m, 2H), 2.80-2.65(m, 1H), 2.00-1.80(m, 2H),1.60-1.40 (m, 4H). TOF-MS [M + H]⁺ 611.0 594

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(4-methoxybenzyl)piperidin-4-yl]ethyl}-9H- purin-6-amine. ¹HNMR(CD₃OD) δ 8.29(s, 1H), 7.40(d, J=6.8 Hz, 2H), 7.28(s, 1H), 7.19 (s,1H), 7.02(d, J=6.8 Hz, 2H), 6.09(s, 2H), 4.36(t, J=7.6 Hz, 2H), 4.20(s,2H), 3.82(s, 3H), 3.50-3.45(m, 2H), 2.98-2.86(m, 2H), 2.16-2.10(m, 2H),1.88-1.80(m, 2H), 1.64-1.54 (m, 1H). TOF-MS [M + H]⁺ 597.0 595

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(4-methoxybenzyl)piperidin-4-yl]ethyl}-3 H- purin-6-amine. ¹HNMR(DMSO-d₆) δ 8.56(s, 1H), 7.46(s, 1H), 7.37(d, J=8.8 Hz, 2H), 7.31 (s,1H), 7.02(d, J=8.8 Hz, 2H), 6.11(s, 2H), 4.27(t, J=7.2 Hz, 2H), 4.17(s,2H), 3.75(s, 3H), 3.32-3.28(m, 2H), 2.80-2.70(m, 2H), 2.00-1.75(m, 3H),1.45-1.25(m, 4H). TOF-MS [M + H]⁺ 597.0 596

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-7-{2-[1-(4-methoxybenzyl)piperidin-4-yl]ethyl}-7H- purin-6-amine. ¹HNMR(CD₃OD) δ 8.19(s, 1H), 7.54(d, J=9.2 Hz, 2H), 7.25(s, 1H), 7.12 (s,1H), 7.09(d, J=9.2 Hz, 2H), 6.09(s, 2H), 4.35-4.25(m, 3H), 3.86(s, 3H),3.50-3.12(m, 4H), 2.10-1.80(m, 4H), 1.48-1.25(m, 4H). TOF-MS [M + H]⁺597.0 597

Benzyl 3-(2-{6-amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carboxylate. LC-MS [M + H]⁺ 611.9 598

Benzyl 3-(2-{6-amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carboxylate. LC-MS [M + H]⁺ 611.9 599

9-[2-(1-Benzylpiperidin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6- amine. ¹H NMR(CD₃OD)68.18(s, 1H), 7.51-7.49(m, 5H), 7.26(s, 1H), 7.09(s, 1H), 6.07(s, 2H),4.34-4.28(m, 2H), 4.27(s, 2H), 3.54-3.48 (m, 2H), 3.00-2.90(m, 2H),2.18-2.10(m, 4H), 1.85-1.80(m, 3H). TOF-MS [M + H]⁺ 567.1 600

3-[2-(1-Benzylpiperidin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6- amine. ¹H NMR(CD₃OD)68.48(s, 1H), 7.51-7.49(m, 5H), 7.34(s, 1H), 7.31(s, 1H), 6.11(s, 2H),4.43-4.38(m, 2H), 4.29(s, 2H), 3.54-3.48 (m, 2H), 3.00-2.90(m, 2H),2.00-0.80(m, 7H). TOF-MS [M + H]⁺ 567.1 601

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(5,5-dimethylmorpholin-2-yl)ethyl]-9H-purin-6- amine. ¹H NMR(Acetone-d₆) δ 8.30(s, 1H), 7.11(s, 1H), 6.92(s, 1H), 6.09(s, 2H), 4.50-4.42(m,2H), 3.70-3.30(m, 5H), 3.00-2.80(m, 2H), 2.94(s, 6H). LC-MS [M + H]⁺507.0 602

4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1- carbaldehyde. ¹H NMR(DMSO-d₆)δ 8.36(s, 1H), 7.95(s, 1H), 7.29(s,1H), 7.10(s, 1H), 6.06 (s, 2H),4.29(t, J=7.6 Hz, 2H), 4.12-4.07(m, 2H), 3.65-3.58(m, 2H), 2.95-2.80(m,2H), 2.64-2.55(m, 1H), 1.92-0.80(m, 4H). TOF-MS [M + H]⁺ 505.0 603

(3R)-3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1-carbaldehyde. LC-MS [M + H]⁺ 505 604

(3R)-3-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde. ¹H NMR(CD₃OD) δ 8.30(s, 1H), 8.01-7.98 (m, 1H), 7.30(s, 1H), 7.20-7.10(m, 1H), 6.10 (s, 2H), 4.40(t,J=7.2 Hz, 2H), 3.70-3.60(m, 2H), 2.90-2.80(m, 2H), 1.90-1.70(m, 5H),1.50-1.30(m, 2H). LC-MS [M + H]⁺ 505 605

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2- [(8-oxabicyclo[3 .2.1]oct-3-yl]ethyl}-9H-purin- 6-amine. ¹H NMR(CD₃OD): δ 8.202 and 8.199(s,1H), 7.265 and 7.262(s, 1H), 7.092 and 7.077(s, 1H), 6.08(s, 2H),4.37-4.30(m, 2H), 4.29-4.24 (m, 2H), 2.17(m, 1H), 2.02-1.75(m, 5H),1.74-1.62(m, 3H), 1.43-1.34(m, 2H); TOF-MS [M+H]⁺ 504.4 606

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2- [(8-oxabicyclo[3 .2.1]oct-3-yl]ethyl}-3H-purin- 6-amine. ¹H NMR(CD₃OD): δ 8.512 and 8.509 (s,1H), 7.384 and 7.376(s, 1H), 7.364 and 7.363 (s, 1H), 6.16 and 6.153(s,2H), 4.39-4.30 (m, 4H), 2.19-2.06(m, 2H), 1.95-1.88(m, 2H), 1.83-1.79(m,2H), 1.78-1.72(m, 2H), 1.62(m, 1H), 1.44-1.32(m, 2H); TOF-MS [M +1]⁺503.8 607

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-methyl-8-oxabicyclo[3.2.1]oct-3-yl]ethyl}- 9H-purin-6-amine. ¹HNMR(CD₃OD): δ 8.251 and 8.248(s, 1H), 7.271 and 7.269(s, 1H), 7.124 and7.112(s, 1H), 6.08(s, 2H), 4.38-4.27(m, 3H), 2.12-2.0 (m, 3H),1.94-1.77(m, 3H), 1.74-1.48(m, 4H), 1.35(m, 1H), 1.29and 1.28(s, 3H);TOF-MS [M +1]⁺ 518.0 608

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2- [1-methyl-8-oxabicyclo[3.2.1 ]oct-3-yl]ethyl}- 3H-purin-6-amine. ¹H NMR(CD₃OD): δ 8.509 and8.507(s, 1H), 7.376 and 7.367(s, 1H), 7.353 (s, 1H), 6.156 and 6.149(s,2H), 4.40-4.32(m, 3H), 2.13-2.08(m, 3H), 1.89-1.48(m, 7H), 1.35(m, 1H),1.295 and 1.291(s, 3H); TOF-MS [M +1]⁺ 518.1 609

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(1-methyl-1H-tetrazol-5-yl)piperidin-4- yl]ethyl}-9H-purin-6-amine.¹H NMR(DMSO- d₆) δ 8.20(s, 1H), 7.65-7.50(brs, 2H), 7.40(s, 1H), 6.85(s,1H), 6.10(s, 2H), 4.22(t, J=7.6 Hz, 2H), 3.85(s, 3H), 3.55(brd, J=12.8Hz, 2H), 2.85(t, J=12.8 Hz, 2H), 1.78(brd, J=12.8 Hz, 2H), 1.70-1.62(m,2H), 1.43(m, 1H), 1.35-1.22(m, 2H); TOF-MS [M + H]⁺ 559.10 610

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(1-ethyl-1H-tetrazol-5-yl)piperidin-4- yl]ethyl}-9H-purin-6-amine. ¹HNMR(CD₃OD) δ 8.24(s, 1H), 7.27(s, 1H), 7.14(s, 1H), 6.08 (s, 2H),4.37(t, J=7.2 Hz, 2H), 4.25(q, J=7.6 Hz, 2H), 3.56(brd, J=12.8 Hz, 2H),2.98(t, J=11.6 Hz, 2H), 1.93(brd, J=12.8 Hz, 2H), 1.84 (brq, 2H),1.57-1.42(m, 3H), 1.51(t, J=7.6 Hz, 3H); TOF-MS [M + H]⁺ 573.11 611

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(1-ethyl-1H-tetrazol-5-yl)piperidin-4- yl]ethyl}-3H-purin-6-amine.1NMR(CD₃OD) δ 8.54(s, 1H), 7.36(s, 1H), 7.45(s, 1H), 6.13 (s, 2H),4.45(t, J=7.6 Hz, 2H), 4.26(q, J=7.6 Hz, 2H), 3.56(brd, J=12.8 Hz, 2H),2.98(t, J=12.4 Hz, 2H), 1.96-1.86(m, 4H), 1.61-1.44(m, 3H), 1.52(t,J=7.6 Hz, 3H); TOF-MS [M + H]^(+573.11) 612

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(1-isopropyl-1H-tetrazol-5-yl)piperidin-4-yl]ethyl}-9H-purin-6-amine. H NMR(CD₃OD) δ 8.21(s, 1H), 7.26(s, 1H),7.11(s, 1H), 6.08 (s, 2H), 4.60(sep, J=6.8 Hz, 1H), 4.34(t, J=7.6 Hz,2H), 3.45(brd, J=12.4 Hz, 2H), 2.96(t, J=12.4 Hz, 2H), 1.93(brd, J=10.8Hz, 2H), 1.82(brq, J=6.4 Hz, 2H), 1.59-1.44(m, 3H), 1.54(d, J=6.8 Hz,6H); TOF-MS [M + H]^(+587.13) 613

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(1-isopropyl-1H-tetrazol-5-yl)piperidin-4-yl]ethyl}-3H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.55(s, 1H), 7.370(s, 1H),7.366(s, 1H), 6.14 (s, 2H), 4.61(sep, J=6.4 Hz, 1H), 4.45(t, J=7.6 Hz,2H), 3.46(brd, J=12.0 Hz, 2H), 2.99(t, J=11.6 Hz, 2H), 1.97-1.86(m, 4H),1.56(d, J=6.4 Hz, 6H), 1.55-1.45(m, 3H); TOF-MS [M + H]⁺ 587.13 614

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(1-tert-butyl-1H-tetrazol-5-yl)piperidin-4-yl]ethyl}-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.21(s, 1H), 7.27(s, 1H),7.10(s, 1H), 6.08 (s, 2H), 4.35(t, J=7.6 Hz, 2H), 3.14(brd, J=12.4 Hz,2H), 2.92(t, J=12.0 Hz, 2H), 1.92 (brd, J=10.0 Hz, 2H), 1.83(brq, J=8.0Hz, 2H), 1.73(s, 9H), 1.58-1.42(m, 3H); TOF-MS [M + H]⁺ 601.1 615

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-(1-tert-butyl-1H-tetrazol-5-yl)piperidin-4-yl]ethyl}-3H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.54(s, 1H), 7.357(s, 1H),7.352(s, 1H), 6.13 (s, 2H), 4.46(t, J=7.6 Hz, 2H), 3.16(brd, J=12.0 Hz,2H), 2.95(t, J=11.6 Hz, 2H), 1.99-1.80(m, 4H), 1.75(s, 9H), 1.58-1.44(m,3H); TOF-MS [M + H]⁺ 601.1 616

4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1- carboximidamide. ¹HNMR(CD₃OD) δ 8.25(s, 1H), 7.28(s, 1H), 7.16(s, 1H), 6.09(s, 2H), 4.36(t,J=7.2 Hz, 2H), 3.87(brd, J=14.0 Hz, 2H), 3.04(td, J=14.0, 2.4 Hz, 2H),1.94(brd, J=12.0 Hz, 2H), 1.84(q, J=7.6 Hz, 2H), 1.65 (m, 1H), 1.30(brq,J=12.0 Hz, 2H); TOF-MS [M + H]⁺ 519.09 617

4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidine-1- carboximidamide. TOF-MS [M +H]⁺ 519.09 618

4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)-N- propylpiperidine-1-carboximidamide. ¹HNMR(CD₃OD) δ 8.33(s, 1H), 7.29(s, 1H), 7.23(s, 1H), 6.10(s, 2H),4.43-4.34(m, 2H), 3.87(brd, J=12.8 Hz, 2H), 3.19(t, J=6.8 Hz, 2H),3.02(t, J=12.0 Hz, 2H), 1.96-1.82(m, 4H), 1.69-1.56(m, 3H), 1.36-1.24(m,2H), 0.97 (t, J=6.8 Hz, 3H); TOF-MS [M + H]⁺ 561.14 619

4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)-N- propylpiperidine-1-carboximidamide. ¹HNMR (CD₃OD) δ 8.55(s, 1H), 7.37(s, 2H), 6.15(s, 2H), 4.44(t, J=7.2 Hz,2H), 3.87(d, J=13.2 Hz, 2H), 3.20(t, J=7.6 Hz, 2H), 3.04(t, J=12.0 Hz,2H), 1.96-1.84(m, 4H), 1.68-1.58(m, 3H), 1.35-1.24(m, 2H), 0.97(t, J=7.6Hz, 3H); TOF-MS [M + H]⁺ 561.14 620

6-({9-[2-(1-Acetylpiperidin-4-yl)ethyl]-6-amino-9H-purin-8-yl}thio)-1,3-benzodioxole-5- carbonitrile. ¹HNMR(CD₃OD) δ 8.31(s, 1H), 7.39(s, 1H), 7.37(s, 1H), 6.21(s, 2H), 4.49(d,J=12.8 Hz, 1H), 4.40(t, J=6.8 Hz, 2H), 3.91(d, J=13.2 Hz, 1H), 3.08(t,J=12.8 Hz, 1H), 2.60(t, J=12.4 Hz, 1H), 2.09(s, 3H), 1.95-1.83(m, 4H),1.62(m, 1H), 1.27(t, J=12.4 Hz, 1H), 1.16(t, J=10.4 Hz, 1H); TOF-MS [M +# H]⁺ 466.16 621

6-({3-[2-(1-Acetylpiperidin-4-yl)ethyl]-6-amino-3H-purin-8-yl}thio)-1,3-benzodioxole-5- carbonitrile. TOF-MS [M +H]⁺ 466.17. 622

2-({9-[2-(1-Acetylpiperidin-4-yl)ethyl]-6-amino-9H-purin-8-yl}thio)-4,5- dimethoxybenzonitrile. ¹H NMR(CD₃OD): δ8.25(s, 1H), 7.47(s, 1H), 7.44(s, 1H), 4.50(brd, J=13.6 Hz, 1H), 4.39(t, J=7.2 Hz, 2H), 3.92(s, 3H), 3.91(s, 3H), 3.90(m, 1H), 3.09(td,J=13.6, 3.2 Hz, 1H), 2.60(td, J=12.4, 2.4 Hz, 1H), 2.09(s, 3H),1.95-1.83(m, 4H), 1.62(m, 1H), 1.25(qd, J=12.0, 4.0 Hz, 1H), 1.15(qd,J=11.6, # 2.8 Hz, 1H); TOF-MS [M + H]⁺ 482.20 623

2-({3-[2-(1-Acetylpiperidin-4-yl)ethyl]-6-amino-3H-purin-8-yl}thio)-4,5- dimethoxybenzonitrile. ¹H NMR(CD₃OD): δ8.53(s, 1H), 7.53(s, 1H), 7.50(s, 1H), 4.52-4.43(m, 1H), 4.39(t, J=7.6Hz, 2H), 3.95(s, 3H), 3.93(s, 3H), 3.85(brd, J=12.8 Hz, 1H), 3.06(td,J=13.6, 2.8 Hz, 1H), 2.58(td, J=12.8, 2.4 Hz, 1H), 2.10(s, 3H),1.94-1.82(m, 4H), 1.6-1.5(m, 1H), 1.16(qd, J=12.4, 4.0 Hz, 1H), 1.06(qd,J=12.0, # 4.0 Hz, 1H); TOF-MS [M + H]⁺ 482.20 624

4-[2-(6-Amino-8-{[6-(methoxymethyl)-1,3-benzodioxol-5-yl]thio}-9H-purin-9- yl)ethyl]piperidine-1-carbaldehyde.¹H NMR(CD₃OD): δ 8.27(s, 1H), 7.99(s, 1H), 7.11(s, 1H), 7.10(s, 1H),6.05(s, 2H), 4.54(s, 2H), 4.35(t, J=8.0 Hz, 2H), 4.3 1-4.27(m, 1H),3.76-3.69(m, 1H), 3.30(s, 3H), 3.14-3.07(m, 1H), 2.66(td, J=12.8, 2.8Hz, 1H), 1.91(td, J=14.4, 2H), 1.80(q, J=7.6 Hz, 2H), 1.62(m, 1H),1.22(qd, J= # 11.2, 3.6 Hz, 1H), 1.20(qd, J=12.4, 4.0 Hz, 1H); TOF-MS[M + H]⁺ 471.21 625

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-prop-2-yn-1-ylpiperidin-4-yl)ethyl]-9H-purin-6- amine. ¹H NMR(CD₃OD): δ8.26(s, 1H), 7.28(s, 1H), 7.16(s, 1H), 6.09(s, 2H), 4.36(t, J=7.6 Hz,2H), 4.1-4.02(m, 2H), 3.68(brd, J=14.0 Hz, 2H), 3.02(brt, J=12.4 Hz,2H), 2.66(s, 1H), 2.21(brd, J=14.8, 2H), 1.9-1.8 1(m, 2H), 1.62-1.60(m,1H), 1.56-1.44(m, 2H); TOF-MS [M + H]⁺ 515.08 626

8-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)-8-azaspiro[4.5]decane-7,9- dione. ¹H NMR(CD₃OD): δ8.30(s, 1H), 7.10 (d, J=2.4 Hz, 1H), 7.06(d, J=8.8 Hz, 1H), 7.01(dd,J=8.8, 3.2 Hz, 1H), 4.53-4.50(m, 2H), 4.25-4.23(m, 2H), 3.77(s, 3H),3.75(s, 3H), 2.53(s, 4H), 1.70-1.66(m, 4H), 1.46-1.42 (m, 4H); LC-MS[M + H]⁺ 497.2 627

8-[(2,5-Dimethoxyphenyl)thio]-9-{2-[4-(1-ethylpropyl)piperazin-1-yl]ethyl}-9H-purin-6- amine. ¹H NMR(CD₃OD): δ8.35(s, 1H), 7.08- 6.98(m, 3H), 4.51(t, J=5.6 Hz, 2H), 3.80(s, 3H),3.76(s, 3H), 3.50-3.36(m, 2H), 3.24-3.12 (m, 2H), 3.09-2.98(m, 3H),2.92(t, J=5.6 Hz, 2H), 2.64-2.5 1(m, 2H), 1.88-1.78(m, 2H), 1.76-1.65(m,2H), 1.033(t, J=6.4 Hz, 6H); TOF-MS [M + H]⁺ 486.27 628

8-[(2,5-Dimethoxyphenyl)thio]-3-{2-[4-(1-ethylpropyl)piperazin-1-yl]ethyl}-3 H-purin-6- amine ¹H NMR(CD₃OD): δ8.52(s, 1H), 7.28(dd, J=2.4, 0.8 Hz, 1H), 7.23-7.18(m, 2H), 4.52(t,J=5.6 Hz, 2H), 3.81(s, 6H), 3.43(brd, J=11.2 Hz, 2H), 3.16(brd, J=12.0Hz, 2H), 3.08-3.00 (m, 3H), 2.94(t, J=5.6 Hz, 2H), 2.54(brt, J=12.0 Hz,2H), 1.89-1.79(m, 2H), 1.76-1.68(m, 2H), 1.05(t, J=7.2 Hz, 6H); # TOF-MS[M + H]^(+486.27) 629

9-[2-(4-Acetylpiperazin-1-yl)ethyl]-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-6-amine. ¹H NMR(CD₃OD): δ 8.21(s, 1H),6.98(d, J=8.8 Hz, 1H), 6.92(d, J=3.2 Hz, 1H), 6.88(dd, J=8.8, 3.2 Hz,1H), 4.43(t, J=5.6 Hz, 2H), 3.77 (s, 3H), 3.70(s, 3H), 3.49(brt, J=4.8Hz, 2H), 3.43(brt, J=4.8 Hz, 2H), 2.85(t, J=5.6 Hz, 2H), 2.50(t, J=4.8Hz, 2H), 2.46(t, J=4.8 Hz, 2H), 2.06(s, 3H); TOF-MS [M + # H]⁺ 458.20630

3-[2-(4-Acetylpiperazin-1-yl)ethyl]-8-[(2,5- dimethoxyphenyl)thio]-3H-purin-6-amine. ¹H NMR(CD₃OD): δ 8.41(s, 1H), 7.19(dd, J=2.0, 1.2 Hz,1H), 7.05-7.04(m, 2H), 4.67(t, J=5.6 Hz, 2H), 3.77(s, 3H), 3.73(s, 3H),3.59(brt, J=4.8 Hz, 2H), 3.56(brt, J=4.8 Hz, 2H), 2.90 (t, J=5.6 Hz,2H), 2.65(t, J=4.8 Hz, 2H), 2.59 (t, J=4.8 Hz, 2H), 2.09(s, 3H); TOF-MS[M + H]⁺ 458.20 631

8-[(2,5-Dimethoxyphenyl)thio]-9-[2-(4-methylpiperazin-1-yl)ethyl]-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.32(s,1H), 7.06-6.98(m, 3H), 4.49(t, J=5.6 Hz, 2H), 3.75(s, 6H), 3.48-3.36(m,2H), 3.21-3.06(m, 2H), 3.00-2.90(m, 2H), 2.88(t, J=5.6 Hz, 2H), 2.84(s,3H), 2.56-2.40(m, 2H); LC-MS [M +H]⁺ 430.5 632

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(4-cyclopentylpiperazin-1-yl)ethyl]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ8.20(s, 1H), 7.21(s, 1H), 7.07(s, 1H), 6.05(s, 2H), 4.43(t, J=5.6 Hz,2H), 4.60-3.65(m, 4H), 3.10-2.42(m, 5H), 2.91 (t, J=5.6 Hz, 2H),2.14-2.04(m, 2H), 1.86-1.76 546.13 633

8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[4-(2,2-dimethylpropanoyl)piperazin-1- yl]ethyl}-9H-purin-6-amine.TOF-MS [M + H]^(+562.11) 634

4-(2-{6-Amino-8-[(2,5-dimethoxyphenyl)thio]-9H-purin-9-yl}ethyl)piperazin-2-one. ¹H NMR (CD₃OD) δ 8.33(s, 1H),7.07(d, J=3.2 Hz, 1H), 7.05(d, J=8.4 Hz, 1H), 7.01(dd, J=8.4, 2.8 Hz,1H), 4.54(t, J=5.6 Hz, 2H), 3.75(s, 3H), 3.74(s, 3H), 3.28-3.24(m, 2H),3.25(s, 2H), 2.98(t, J=5.6 Hz, 2H), 2.83(t, J=5.2 Hz 2H); LC-MS [M + H]⁺430.5 635

8-[(2,5-Dimethoxyphenyl)thio]-9-(2-morpholin-4-ylethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.40(s, 1H), 7.17(dd,J=2.0, 1.6 Hz, 1H), 7.05-7.04(m, 2H), 4.74(t, J=5.6 Hz, 2H),3.78-3.75(m, 7H), 3.73(s, 3H), 3.06(t, J=5.6 Hz, 2H), 2.9-2.8(m, 4H);LC-MS[M + H]⁺ 417.5 636

8-[(2,5-Dimethoxyphenyl)thio]-3-(2-morpholin-4-ylethyl)-3H-purin-6-amine. LC-MS [M + H]^(+417.5) 637

tert-Butyl 3-(3-{6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-9H-purin-9- yl}propyl)piperidine-1-carboxylate. LC-MS [M +H]⁺ 591.5 638

tert-Butyl 2-(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}propyl)piperidine-1-carboxylate.LC-MS [M + H]⁺ 591.5 639

tert-Butyl 4-({6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-9H-purin-9- yl}methyl)piperidine-1-carboxylate. LC-MS [M +H]⁺ 563.4 640

tert-Butyl 4-({6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-3H-purin-3- yl}methyl)piperidine-1-carboxylate. LC-MS [M +H]⁺ 563.4 641

tert-Butyl 3-({6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-9H-purin-9- yl}methyl)piperidine-1-carboxylate. LC-MS [M +H]⁺ 563.4 642

tert-Butyl 3-({6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-3H-purin-3- yl}methyl)piperidine-1-carboxylate. LC-MS [M +H]⁺ 563.4 643

Diethyl [2-(2-{6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]phosphonate. LC-MS [M +H]⁺ 613.4 644

Diethyl [4-(2-{6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]phosphonate. LC-MS [M +H]⁺ 613.4 645

tert-Butyl [2-(2-{6-amino-8-[(6-bromo-1,3- benzodioxo1-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]acetate. LC-MS [M + H]⁺+591.4

Example 646

8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(3-piperidin-2-ylpropyl)-9H-purin-6-amine

The title compound was prepared according to the procedure described forexample 465 using product obtained from example 638. LC-MS [M+H]⁺ 491.4

Example 647

8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(3-piperidin-3-ylpropyl)-9H-purin-6-amine

The title compound was prepared according to the procedure described forexample 465 using product obtained from example 637. LC-MS [M+H]⁺ 491.4

Example 648

8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(piperidin-4-ylmethyl)-9H-purin-6-amine

The title compound was prepared according to the procedure described forexample 465 using product obtained from example 639. LC-MS [M+H]⁺ 463.3

Example 649

8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(piperidin-3-ylmethyl)-9H-purin-6-amine

The title compound was prepared according to the procedure described forexample 465 using product obtained from example 641. LC-MS [M+H]⁺ 463.3

Example 650

[2-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]aceticacid

The title product was prepared according to the procedure described forexample 465 using product obtained from example 645. LC-MS [M+H]⁺ 535.4

Example 651

Reagents: a) Barton's base, THF, 100° C., MW, 15 min; b) t-BuOK, DMF,90-100° C., 6 h

Step 1: 9-[2-(1-acetylpiperidin-4-yl)-ethyl]-8-bromo-9H-purin-6-amineand 3-[2-(1-acetylpiperidin-4-yl)-ethyl]-8-bromo-3H-purin-6-amine.

To a suspension of 8-bromoadenine (0.042 g, 0.197 mmol) andtoluene-4-sulfonic 2-(1-acetyl-piperidin-4-yl)-ethyl ester (0.077 g,0.237 mmol) in THF was added Barton's base (50 μl, 0.237 mmol) at roomtemperature. The reaction mixture was heated at 100° C. for 15 min inmicrowave reactor, at the end of this period reaction was cooled to roomtemperature and the crude was purified by Isco silica gel flash columnusing 0-5% gradient of methanol in dichloromethane to give 0.030 g (42%)of 9-[2-(1-acetylpiperidin-4-yl)-ethyl]-8-bromo-9H-purin-6-amine, LC-MS[M+H]⁺ 366.2 and 0.015 g (21%) of3-[2-(1-acetylpiperidin-4-yl)-ethyl]-8-bromo-3H-purin-6-amine, LC-MS[M+H]⁺ 366.2

Step 2:9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(6-nitro-1,3-benzothiazol-2-yl)thio]-9H-purin-6-amine

Reagents: a) t-BuOK, 5-nitro-2-mercaptobenzothiazole, DMF, 90-100° C., 6h

To a suspension of 5-nitro-2-mercaptobenzothiazole (0.040 g, 0.246 mmol)in DMF (1.0 mL) was added (CH₃)₃COK (0.028 g, 0.246 mmol) at roomtemperature and stirring continued for 30 min. To the above reactionmixture 9-[2-(1-acetylpiperidin-4-yl)-ethyl]-8-bromo-9H-purin-6-amine(0.030 g, 0.082 mmol) in (1 mL) of DMF was added at room temperature.The reaction mixture was heated to 130° C. for 6 h, at the end of thisperiod solvent was evaporated and crude was purified by preparative HPLC[X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobile phase: solvent A:Water HPLC grade containing 0.01% TFA, and solvent B: acetonitrilecontaining 0.01% TFA, general eluting gradient—solvent B 15% to 80 over15 to 25 minutes run time]. After lyophilization of HPLC fractions toafford title product.9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(6-nitro-1,3-benzothiazol-2-yl)thio]-9H-purin-6-amine.¹H NMR (CD₃OD) δ 8.80 (s, 1H), 8.30 (d, J=2.4 Hz, 1H), 8.00 (d, J=9.2Hz, 1H), 7.84 (s, 1H), 4.80 (t, J=7.6 Hz, 2H), 3.90-3.80 (m, 2H),3.20-3.10 (m, 3H), 3.10-2.60 (m, 3H), 2.00 (s, 3H), 1.94-1.80 (m, 3H).LC-MS [M+H]⁺ 499.13

Examples 652-661 were prepared according to the procedure described forexample 651 using appropriate starting materials and their analyticaldata is summarized in table 11. All the compounds were isolated as atrifluoroacetate salt after preparative HPLC purification. TABLE 11Example Structure Name and analytical data 652

3-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(6-nitro-1,3-benzothiazol-2-yl)thio]-3H-purin- 6-amine. ¹H NMR(CD₃OD) δ8.90(d, J=2.4Hz, 1H), 8.36(dd, J=8.8, 2.4 Hz, 1H), 8.30(s, 1H), 8.01(d, J=8.8 Hz,1H), 4.40(t, J=7.6 Hz, 2H), 3.90-3.80(m, 2H), 3.00-2.91(m, 2H),2.51-2.43(m, 2H), 2.02(s, 3H), 1.82-1.72(m, 3H), 1.55-1.49(m, 2H). LC-MS[M + H]⁺ 499.13 653

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(4-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin- 6-amine. ¹H NMR(CD₃OD) δ8.30(s, 1H),7.80(d, J=8.8 Hz, 1H), 7.50(d, J=8.8 Hz, 1H), 7.40-7.30(m, 1H), 4.40(t,J=7.6 Hz, 2H), 3.80-3.78(m, 2H), 3.00-2.90(m, 2H), 2.50-2.40(m, 2H),2.35-2.15(m, 2H), 2.00(s, 3H), 1.80-1.70(m, 3H). LC-MS [M + H]^(+488.10)654

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(4,5-dimethyl-1,3-thiazol-2-yl)thio]-9H-purin-6- amine. ¹H NMR(CD₃OD) δ 8.50 (s, 1H),4.40(t, J=7.2 Hz, 2H), 3.90-3.87(m, 2H), 2.60-2.5 1(m, 2H), 2.50(s, 3H),2.30(s, 3H), 2.00(s, 3H), 1.90-1.80(m, 3H), 1.70-1.60(m, 2H),1.60-1.50(m, 2H). LC-MS [M + H]⁺ 432.10 655

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(6-fluoro-1,3-benzothiazol-2-yl)thio]-9H-purin- 6-amine. ¹H NMR(CD₃OD) δ8.40(s, 1H),7.90-7.80(m, 1H), 7.74-7.70(m, 1H), 7.33-7.30(m, 1H), 4.50(t, J=7.2 Hz,2H), 3.80-3.70(m, 1H), 3.00-2.90(m, 2H), 2.00(s, 3H), 1.80-1.70(m, 4H),1.50-1.40(m, 2H), 1.20-1.00(m, 2H). LC-MS [M + H]⁺ 472.14 656

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(5-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin- 6-amine. LC-MS [M + H]⁺ 488.01 657

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin- 6-amine. ¹H NMR(CD₃OD) δ8.30(s, 1H),7.85-7.83(m, 1H), 7.50-7.40(m, 2H), 4.50(t, J=7.2 Hz, 2H), 3.83-3.80(m,2H), 3.00-2.90(m, 2H), 2.50-2.40(m, 2H), 2.10(s, 3H), 2.00-1.90(m, 3H),1.50-1.40(m, 2H). LC-MS [M + H]^(+488.12) 658

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-[(5-methoxy-1,3-benzothiazol-2-yl)thio]-9H-purin- 6-amine. ¹H NMR(CD₃OD) δ8.30(s, 1H),7.70(d, J=8.8 Hz, 1H), 7.40(d, J=2.4 Hz, 1H), 7.00 (dd, J=8.8, 2.4 Hz,J=8.8 Hz, 1H), 4.40(t, J=7.6 Hz, 2H), 3.90 (s, 3H), 3.50-3.40(m, 2H),3.14-3.12(m, 2H), 2.20(s, 3H), 1.72-1.70(m, 3H), 1.30-1.20(m, 4H). LC-MS[M + H]⁺ 484.15 659

9-[2-(1-Acetylpiperidin-4- yl)ethyl]-8-(1,3-benzothiazol-2-ylthio)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.30(s, 1H), 7.93-7.90(m, 2H),7.50-7.40(m, 2H), 4.40(t, J=7.6 Hz, 2H), 3.81-3.80(m, 2H), 3.14-3.12(m,2H), 3.00-2.90(m, 2H), 2.20(s, 3H), 1.80-1.70(m, 2H), 1.50-1.40(m, 3H).LC-MS [M + H]⁺ 454.15 660

2-[2-({9-[2-(1-Acetylpiperidin-4- yl)ethyl]-6-amino-9H-purin-8-yl}thio)-4-methyl-1,3-thiazol-5- yl]acetamide. LC-MS [M + H]^(+475.16.)661

4-(2-{6-Amino-8-[(7-chloro-1,3- benzothiazol-2-yl)thio]-9H-purin-9yl}-ethyl)-piperidin-1- carbaldehyde. LC-MS [M + H]^(+474.0)

Intermediate 115

Methanesulfonic acid3-tert-butoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-propyl ester

To a solution of [3-hydroxy-1-(tetrahydro-pyran-4-yl)-propyl]-carbamicacid tert-butyl ester (0.200 g, 0.770 mmol) and NEt₃ (192 μL, 0.920mmol) in CH₂Cl₂ (8 mL) was added MsCl (72 μL, 0.92 mmol) at 0° C. andthe mixture was stirred at room temperature for 10 h. The solvent wasevaporated to dryness and EtOAC was added. The ethyl acetate layer waswashed with aq. NaHCO₃, dried (Na₂SO₄), filtered, and solvent wasevaporated under reduced pressure to afford methanesulfonic acid3-tert-butoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-propyl ester (0.162g). LC-MS [M+Na] 360.2. The product was sufficiently pure for the nextstep and used without further purification.

Intermediate 116

Methanesulfonic acid 3-cyclopropyl-3-methanesulfonylamino-propyl ester

The title compound (0.120 g) was prepared fromN-(1-cyclopropyl-3-hydroxy-propyl)-methanesulfonamide according to theprocedure described intermediate 115. The product was used for the nextstep without further purifications.

Intermediate 117

Methanesulfonic acid 3-tert-butoxycarbonylamino-3-cyclobutyl-propylester

To a solution of 3-tert-butoxycarbonylamino-3-cyclobutyl-propionic acid(0.300 g, 1.23 mmol) in THF (12 mL) was added BH₃—SMe₂ (1.70 mL, 3.33mmol; 2.0 M solution in THF) at 0° C. After stirring at rt for 10 h, thereaction mixture was quenched with satd. NaHCO₃, extracted with EtOAc,washed with brine, dried (Na₂SO₄), and concentrated in vacuo to afford(1-cyclobutyl-3-hydroxy-propyl)-carbamic acid tert-butyl ester (0.100g); LC-MS [M+H]⁺ 230.0. The product is sufficiently pure for the nextstep and used for the next step without further purification.

The title product (0.082 g) was prepared using the above alcohol bysimilar procedure described for intermediate 115. LC-MS [M+H]⁺ 308.3.

Intermediate 118

1-(3-Bromo-1-cyclopropyl-propyl)-3-isopropyl-urea

To a solution of 3-amino-3-cyclopropan-1-ol hydrochloride (0.25 g, 1.65mmol) and NEt₃ (690 μL, 4.95 mmol) in CH₃CN (5 mL) was added2-isocyanatopropane (180 μL, 1.80 mmol) at 0° C. After stirring for 10 hat rt, the reaction mixture was quenched with H₂O and extracted withEtOAC, washed with brine, dried (Na₂SO₄), filtered, and concentrated invacuo to furnish 1-(1-cyclopropyl-3-hydroxy-propyl)-3-isopropyl-urea(0.189 g).

The 1-(1-cyclopropyl-3-hydroxy-propyl)-3-isopropyl-urea (0.189 g, 0.950mmol) was then dissolved in CH₂Cl₂ (10 mL) and CBr₄ (0.477 g, 1.40 mmol)was added and the mixture was cooled to 0° C. To the mixture was addedPPh₃-polymer-bound resin (0.889 g, 1.40 mmol; 1.6 mmol/g) inportionwise. After stirring for at rt for 3 h, the mixture was dilutedwith CH₂Cl₂ (50 mL), filtered, and washed with CH₂Cl₂/MeOH/Acetone. Thecombined filtrates were concentrated in vacuo to give1-(3-Bromo-1-cyclopropyl-propyl)-3-isopropyl-urea (0.212 g). GC-MS m/z262.

Examples 662 and 663 tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)carbamateand tert-butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)carbamate

A mixture of8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine (0.145 g,0.396 mmol), (3-bromo-1-cyclopropyl-propyl)-carbamic acid tert-butylester (0.228 g, 0.82 mmol), and Barton's base (0.140 g, 0.82 mmol) inDMF (4 mL) was heated at 80-100° C. for 6-15 h. After cooling, thereaction mixture was concentrated under reduced pressure. The residuewas purified by preparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm(waters), Mobile phase: solvent A: Water HPLC grade containing 0.01%TFA, and solvent B: acetonitrile containing 0.01% TFA, general elutinggradient—solvent B 15% to 80 over 15 to 25 minutes run time]. Afterlyophilization of HPLC fractions N-9 and N-3 isomers were isolated astrifluoroacetate salts. tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)carbamate.¹H NMR (DMSO-d₆)

8.17 (s, 1H), 7.37 (s, 1H), 6.79 (s, 1H), 6.10 (s, 2H), 4.20-4.19 (m,2H), 2.90-2.85 (m, 2H), 2.00-1.80 (m, 2H), 1.38 (s, 9H), 0.40-0.20 (m,4H); LC-MS [M+H]⁺ 563.10. tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)carbamate.¹H NMR (DMSO-d₆) δ 8.49 (s, 1H), 7.51 (s, 1H), 7.40 (s, 1H), 6.18 (s,2H), 4.35-4.30 (m, 2H), 2.92-2.85 (m, 2H), 2.20-1.50 (m, 6H), 1.38 (s,9H); LC-MS [M+H]⁺ 563.10.

Examples 664-685 were synthesized analogously to the procedure describedfor examples 662 and 663 using appropriate starting materials and areisolated as a trifluoroacetate salt after preparative HPLC purification.TABLE 12 Example # Structure Name and analytical data 664

tert-Butyl(3-{6-amino-8-[(2,5- dimethoxyphenyl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)carbamate. ¹H NMR(DMSO-d₆) δ 8.26(s, 1H), 7.03 (d,J=9.2 Hz, 1H), 6.89-6.86(m, 2H), 6.52(s, 1H), 4.30-4.15(m, 2H), 3.74(s,3H), 3.70-3.50(m, 2H), 3.62(s, 3H), 2.85-2.80(m, 1H), 2.05-1.85(m, 1H),1.36(s, 9H), 0.40-0.20(m, 4H); LC-MS [M + H]⁺ 501.2. 665

tert-Butyl(3-{6-amino-8-[(2,5- dimethoxyphenyl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)carbamate LC-MS [M + H]⁺ 501.2 666

tert-Butyl[3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}-1-(tetrahydro-2H-thiopyran-4-yl)propyl]carbamate. ¹H NMR(DMSO d₆) δ 8.26(s, 1H), 7.39(s, 1H), 6.81(s,1H), 6.09(s, 2H), 4.20-4.10(m, 2H), 3.45-3.30(m, 2H), 2.54-2.49(m, 2H),1.90-1.70(m, 4H), 1.38(s, 9H), 1.30-1.10(m, 4H); TOF LC-MS [M +H]^(+623.1.) 667

tert-Butyl[3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}-1-(tetrahydro-2H-thiopyran-4-yl)propyl]carbamate. LC-MS[M + H]^(+623.1) 668

tert-Butyl[3-{6-amino-8-[(2,5- dimethoxyphenyl)thio]-9H-purin-9-yl}-1-(tetrahydro-2H-thiopyran-4- yl)propyl]carbamate. ¹H NMR (Acetone-d₆) δ8.35(s, 1H), 7.06(d, J=8.4 Hz, 1H), 6.93(dd, J=8.4 Hz, 2.8 Hz, 1H),6.76(d, J=2.8 Hz, 1H), 4.40-4.30(m, 2H), 3.83(s, 3H), 3.69(s, 3H),3.50-3.40(m, 1H), 2.65-2.50(m, 5H), 2.10-1.80(m, 4H), 1.41(s, 9H); LC-MS[M + H]⁺ 561.05. 669

tert-Butyl[3-{6-amino-8-[(2,5- dimethoxyphenyl)thio]-3H-purin-3-yl}-1-(tetrahydro-2H-thiopyran-4- yl)propyl]carbamate. ¹H NMR (Acetone-d₆) δ8.50(s, 1H), 7.29(d, J=2.8 Hz, 1H), 7.01(d, J=8.8 Hz, 1H), 7.03(dd,J=8.8, 2.8 Hz, 1H), 4.50-4.39 (m, 2H), 3.81(s, 3H), 3.79(s, 3H),3.58-3.50(m, 4H), 2.65-2.50(m, 3H), 2.10-1.80(m, 5H), 1.41(s, 9H); LC-MS[M + H]⁺ 561.3. 670

tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}-1-cyclohexylpropyl)carbamate.¹H NMR(DMSO-d₆) δ 8.18(s, 1H), 7.37 (s, 1H), 6.70(s, 1H), 6.08(s, 2H),4.17-4.15(m, 2H), 3.30-3.20(m, 2H), 2.50-2.40(m, 2H), 1.80-1.50(m, 6H),1.38 (s, 9H), 1.20-0.80(m, 4H); LC-MS [M + H]⁺ 605.1. 671

tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}-1-cyclohexylpropyl)carbamate.¹H NMR(DMSO-d₆) δ 8.46(s, 1H), 7.50 (s, 1H), 7.38(s, 1H), 6.18(s, 2H),4.33-4.22(m, 2H), 3.27-3.15(m, 2H), 2.50-2.40(m, 2H), 1.80-1.50(m, 6H),1.39 (s, 9H), 1.20-0.80(m, 4H); LC-MS [M + H]⁺ 605.1. 672

tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}-1-cyclobutylpropyl)carbamate.¹H NMR(CD₃OD) δ 8.25(s, 1H), 7.26(s, 1H), 7.16(s, 1H), 6.08(s, 2H),4.40-4.28(m, 2H), 3.49-3.4(m, 4H), 1.90-1.50(m, 6H), 1.43(s, 9H); LC-MS[M + H]⁺ 577.1. 673

tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3- yl}-1-cyclobutylpropyl)carbamate.¹H NMR(CD₃OD) δ 8.41(s, 1H), 7.35(s, 1H), 7.30(s, 1H), 6.14(s, 2H),4.40-4.28(m, 2H), 3.57-3.52(m, 4H), 1.90-1.60(m, 6H), 1.43(s, 9H); LC-MS[M + H]⁺ 577.1 674

N-(3-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}- 1-cyclopropylpropyl)methanesulfonamide ¹H NMR(Acetone-d₆) δ 8.39(s, 1H),7.27(s, 1H), 7.05(s, 1H), 6.14(s, 2H), 4.54-4.40(m, 2H), 3.30-3.20(m,1H), 3.02(s, 3H), 2.98-2.87(m, 3H), 2.20-2.19(m, 2H), 2.08-2.04(m, 2H);TOF LC-MS[M + H]⁺ 541.4 675

N-(3-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}- 1-cyclopropylpropyl)methanesulfonamide. ¹H NMR(Acetone-d₆) δ 8.56(s, 1H),7.34(s, 1H), 7.28(s, 1H), 6.17(s, 2H), 4.59-4.50(m, 2H), 3.30-3.20(m,1H), 3.10-3.04(m, 6H), 3.01(s, 3H), 2.98-2.87(m, 1H); TOF LC-MS[M +H]^(+541.4.) 676

N-(3-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-9H-purin-9-yl}- 1-cyclopropylpropyl)methanesulfonamide ¹H NMR(Acetone-d₆) δ 8.38(s, 1H),7.06(d, J=7.6Hz, 1H), 6.96(d, J=7.6 Hz, 1H), 6.87(s, 1H), 4.52-4.47(m,2H), 3.81(s, 3H), 3.71(s, 3H), 3.30(s, 3H), 2.90-2.80(m, 3H),2.20-2.00(m, 4H), 1.10-1.00(m, 1H), LC-MS [M + H]⁺ 479.4. 677

N-(3-{6-Amino-8-[(2,5- dimethoxyphenyl)thio]-3H-purin-3-yl}- 1-cyclopropylpropyl)methanesulfonamide ¹H NMR(Acetone-d₆) δ 8.56(s, 1H),7.26(d, J=2.8Hz, 1H), 7.08(d, J=9.2 Hz, 1H), 7.01(dd, J=9.2, 2.8Hz, 1H),4.59-4.53(m, 2H), 3.80(s, 3H), 3.79(s, 3H), 3.30-3.04(m, 6H),1.90-1.70(m, 5H); LC-MS[M + H]⁺ 479.4. 678

N-(3-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclopropylpropyl)-N′-isopropylurea ¹H NMR(DMSO-d₆) δ 8.28(s, 1H),7.39(s, 1H), 6.91(s, 1H), 6.10(s, 2H), 5.72-5.70(m, 1H), 5.61-5.58(m,1H), 4.22(t, J=7.6 Hz, 2H), 3.11-3.08(m, 2H), 1.94-1.84(m 1H),1.02-0.99(m, 6H),0.83-0.80(in, 2H), 0.40-0.11(m, 4H); LC-MS[M + H]⁺548.3 679

N-(3-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}-1-cyclopropylpropyl)-N′-isopropylurea. LC-MS[M + H]⁺ 548.4 680

{3-[6-Amino-8-(6-bromo- benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-cyclopentyl-propyl}-carbamic acid tert-butyl ester. ¹H NMR(Acetoned₆) δ 8.43(s, 1H), 7.46(s, 1H), 6.81(s, 1H), 6.14(s, 2H), 4.35-4.20(m,2H), 3.20-3.18(m, 3H), 1.84-1.40(m, 9H), 1.37(s, 9H); LC-MS[M + H]⁺591.1 681

{3-[6-Amino-8-(6-bromo- benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-cyclopentyl-propyl}-carbamic acid tert-butyl ester. ¹HNMR(Acetone- d₆) δ 8.16(s, 1H), 7.34(s, 1H), 6.74(s, 1H), 6.06(s, 2H),4.17-4.10(m, 2H), 3.38-3.20(m, 3H), 1.80-1.40(m, 9H), 1.36(s, 9H); TOFLC-MS[M + H]^(+591.14) 682

[3-[6-Amino-8-(6-bromo- benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(tetrahydro-pyran-4-yl)-propyl]- carbamic acid tert-butyl ester.¹H NMR (Acetone-d₆) δ 8.19(s, 1H), 7.36(s, 1H), 6.76(s, 1H), 6.06(s,2H), 4.20-4.10(m, 2H), 3.80-3.70(m, 3H), 3.25-3.10(m, 4H), 2.50-2.40(m,5H), 1.36 (s, 9H); LC-MS[M + H]⁺ 607.1 683

[3-[6-Amino-8-(6-bromo- benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-3-yl]-1- (tetrahydro-pyran-4-yl)-propyl]- carbamic acid tert-butylester. ¹H NMR (Acetone-d₆) δ 8.45(s, 1H), 7.48(s, 1H), 6.81(s, 1H),6.15(s, 2H), 4.35-4.20(m, 2H), 3.80-3.70(m, 3H), 3.25-3.10(m, 4H),2.50-2.40(m, 5H), 1.37 (s, 9H); LC-MS[M + H]⁺ 607.1 684

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[3-cyclohexyl-3-(1H-pyrrol-1-yl)propyl]-9H-purin-6-amine. ¹H NMR (CD₃OD) δ 8.23(s, 1H), 7.26(s,1H), 7.08(s, 1H), 6.70-6.80(m, 2H), 6.07(s, 2H), 6.04-6.02(m, 2H),4.23-4.16(m, 2H), 3.95-3.85(m, 1H), 3.78-3.70(m, 2H), 2.38-2.38(m, 2H),1.80-1.70 (m,3H), 1.68-1.55(m, 4H), 1.30-1.10 (m, 2H); LC-MS[M + H]⁺555.1 685

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[3-cyclohexyl-3-(1H-pyrrol-1-yl)propyl]-3H-purin-6-amine. ¹H NMR (CD₃OD) δ 7.93(s, 1H), 7.30(s,1H), 7.25(s, 1H), 6.59(m, 2H), 6.11(s, 2H), 6.00-5.98(m, 2H), 4.204.09(m, 2H), 3.70-3.60(m, 2H), 3.36-3.25(m, 1H), 2.60-2.40(m, 2H),1.81-1.70(m, 3H), 1.65-1.51(m, 4H), 1.30-1.10(m, 2H); LC-MS[M + H]⁺555.1

Example 6869-(3-Amino-3-cyclobutylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine

To a solution of tert-Butyl(3-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}-1-cyclobutylpropyl)carbamate(0.015 g, 0.026 mmol) in EtOAc (2 mL) was added dropwise conc. HCl (1mL) and the resulting mixture was stirred for overnight at roomtemperature. After concentration under reduced pressure, the residualHCl was removed by co-evaporation with toluene afford title product(0.005 g) as a hydrochloride salt. ¹H MNR (CD₃OD) δ 8.33 (s, 1H), 7.29(s, 1H), 7.19 (s, 1H), 6.09 (s, 2H), 4.40-4.28 (m, 2H), 3.49-3.40 (m,4H), 2.50-1.70 (m, 6H); LC-MS [M+23]⁺ 477.9.

Examples 687-692 were synthesized in the same manner as described forexample 686 using appropriate starting materials and are isolated as ahydrochloride salts. TABLE 13 Example Structure Analytical data 687

9-(3-Amino-3-cyclopropylpropyl)-8- [(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.30(s, 1H), 7.41(s, 1H),6.93(s, 1H), 6.11(s, 2H), 4.35 (t, J=7.6 Hz, 2H), 2.56-2.52(m, 1H),2.20-2.00(m, 2H), 0.95-0.80 (m, 1H), 0.64-0.4 1(m, 4H); LC-MS [M + H]⁺463.0 688

3-(3-Amino-3-cyclopropylpropyl)-8- [(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine. ¹H NMR (DMSO-d₆) δ 8.56(s, 1H), 7.94(s, 1H),7.47(s, 1H), 6.16(s, 2H), 4.44 (t, J=7.2 Hz, 2H), 2.5 1-2.49(m, 1H),2.32-2.29(m, 2H), 0.95-0.84 (m, 1H), 0.59-0.40(m, 4H); LC-MS [M + H]⁺463.0 689

9-[3-Amino-3-(tetrahydro-2H- thiopyran-4-yl)propyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹H NMR(DMSO-d₆) δ 8.36(s,1H), 7.42(s, 1H), 6.91(s, 1H), 6.11(s, 2H), 4.42-4.22(m, 2H),3.10-3.6(m, 2H), 2.67-2.52(m, 4H), 1.9-1.8(m, 4H), 1.43-1.20(m, 2H);LC-MS[M + H]⁺ 523.0 690

9-(3-Amino-3-cyclohexylpropyl)-8- [(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine. ¹H NMR δ (DMSO-d₆) 8.22(s, 1H), 7.40(s, 1H),6.78(s, 1H), 6.08(s, 2H), 4.17-4.15(m, 2H), 3.30-3.20(m, 2H),2.33-2.30(m, 2H), 1.80-1.50(m, 6H), 1.20-0.80(m, 4H); LC-MS [M + H]⁺505.1. 691

9-(3-Amino-3-cyclopentyl-propyl)- 8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine. ¹H NMR(Acetone-d₆) δ 8.18(s, 1H),7.36(s, 1H), 6.77(s, 1H), 6.07(s, 2H), 4.35-4.25(m, 2H), 3.38-3.20 (m,3H), 1.70-1.50(m, 9H); LC-MS [M + H]⁺ 491 692

9-[3-Amino -3 -(tetrahydro-pyran-4- yl)-propyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H- purin-6-ylamine ¹H NMR(Acetone d₆) δ8.36(s, 1H), 7.39(s, 1H), 6.89 (s, 1H), 6.09(s, 2H), 4.4-4.25(m, 2H),3.87-3.85(m, 3H), 3.25-3.19 (m, 4H), 1.98-1.96(m, 4H); LC-MS [M + H]⁺507.0

Intermediate 119

Toluene-4-sulfonic acid2-[1-((S)-2-tert-butoxycarbonylamino-propionyl)-piperidin-4-yl]-ethylester

Reagents: (a) N-boc-L-Ala-OSu, Et₃N, DMF, 120° C., (b) p-TsCl, Et₃N,cat. DMAP, THF.

To a solution of 4-piperidine ethanol (0.25 g, 1.93 mmol) and NEt₃ (403μL, 2.89 mmol) in DMF (3 mL) was added N-boc-L-Ala-Osu (0.553 g, 193mmol) at rt and the mixture was stirred at 120° C. temperature for 10 h.The reaction mixture was diluted with EtOAc (60 mL). The ethyl acetatelayer was washed with H₂O (60 mL) and brine (60 mL), dried over Na₂SO₄,filtered, and solvent was evaporated under reduced pressure to afford{(S)-2-[4-(2-Hydroxy-ethyl)-piperidin-1-yl]-1-methyl-2-oxo-ethyl}-carbamicacid tert-butyl ester (0.581 g). LC-MS [M+H]⁺ 301.0. The product wassufficiently pure for the next step and used without furtherpurification. To the mixture of alcohol (0.581 g, 1.93 mmol), triethylamine (808 μL, 5.8 mmol), N,N-dimethylpyridine (10 mg) in THF (10 mL)was added p-TsCl (0.479 g, 2.51 mmol) at room temperature and stirredthe reaction mixture for 12 h. The reaction mixture was concentratedunder vacuum and diluted with EtOAc (90 mL), washed with sat. aq. NaHCO₃solution (75 mL), H₂O (75 mL) and brine (75 mL). The EtOAc layer wasdried over Na₂SO₄, filtered, and solvent was evaporated under reducedpressure to afford crude product. The crude was purified by Isco silicagel flash column using Hexane-EtOAc (1:3) to give puretoluene-4-sulfonic acid2-[1-((S)-2-tert-butoxycarbonylamino-propionyl)-piperidin-4-yl]-ethylester (0.805 g). ¹H NMR (CDCl₃) δ 7.79 (d, J=8.2 Hz, 2H), 7.36 (d, J=8.2Hz, 2H), 5.55 (d, J=7.8 Hz, 1H), 4.62-4.50 (m, 2H), 4.06 (q, J=6.2 Hz,2H), 3.88-3.75 (m, 1H), 2.97 (q, J=12.1 Hz, 1H), 2.53 (dt, J=2.7, 12.8Hz, 1H), 2.46 (s, 3H), 1.75-1.55 (m, 4H), 1.49-1.40 (m, 10H), 1.27 (d,J=7.0 Hz, 3H), 1.12-0.98 (m, 2H); LC-MS [M+H]⁺ 455.2.

Intermediate 120

Toluene-4-sulfonic acid2-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-ethyl ester

Reagents: (a) Me₂NCH₂COOH, EDCI, DMAP, DMF. (b) p-TsCl, Et₃N, cat. DMAP,THF

To the mixture of N,N-dimethylamino pyridine (1.18 g, 9.66 mmol), EDCI(1.48 g, 7.73 mmol), in DMF (5 mL) was added carboxylic acid (0.398 g,3.86 mmol), then followed by the addition of 4-piperadinethanol (0.5 g,3.86 mmol). The reaction mixture was allowed to stir at room temperaturefor 12 h. The reaction mixture was diluted with EtOAc (75 mL) and washedwith brine (60 mL). The EtOAc layer was dried over Na₂SO₄, filtered, andsolvent was evaporated under reduced pressure to afford crude amide. Thecrude was used for the next tosylation reaction without furtherpurification. To the above crude product (0.827 g, 3.86 mmol), triethylamine (3.22 mL, 23.18 mmol), in THF (20 mL) was added tosyl chloride(2.21 g, 11.59 mmol) at room temperature and stirred for 12 h. Thereaction mixture was concentrated in vacuo and the crude was dissolvedin EtOAc (100 mL), washed with sat. aq. NaHCO₃ solution (90 mL),followed by brine (90 mL). The EtOAc layer was dried over Na₂SO₄,filtered, and solvent was evaporated under reduced pressure to affordcrude product, which was purified by Isco silica gel flash column usingHexane-EtOAc (1:9) to obtain 0.45 g of toluene-4-sulfonic acid2-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-ethyl ester. LC-MS [M+H]⁺369.2

Intermediate 121

Acetic acid(S)-1-methyl-2-oxo-2-{4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethylester

Reagents: a) (S)-CH₃CH(OCOCH₃)COCl, NEt₃, THF; b) p-TsCl, Et₃N, cat.DMAP, THF

To the mixture of piperidine ethanol (2 g, 15.5 mmol), triethylamine(4.3 mL, 31.0 mmol) in tetrahydrofuran (15 mL) at room temperature wasadded acetic acid (S)-1-chlorocarbonyl-ethyl ester (2.1 mL, 17.0 mmol)drop wise. The reaction mixture was allowed to stir at room temperaturefor 8 h, The reaction mixture was dissolved in ethyl acetate (100 mL)and washed with sat. aq. NaHCO₃ solution (90 mL) followed by brinesolution (90 mL). The ethyl acetate layer was dried over Na₂SO₄,filtered, and solvent was evaporated under reduced pressure to affordcrude product (1.6 g), which was used in next tosylation reactionwithout further purification. The crude obtained in the previous stepwas dissolved in tetrahydrofuran (20 mL) and added triethyl amine (2.28mL, 16.4 mmol), N,N-dimethylpyridine (20 mg) followed by p-TsCl (1.5 g,7.9 mmol) at room temperature and stirred the reaction mixture for 12 h.The reaction mixture was concentrated in vacuo and diluted with EtOAc(90 mL), washed with sat. aq. NaHCO₃ solution (75 mL), H₂O (75 mL) andbrine (75 mL). The EtOAc layer was dried over Na₂SO₄, filtered, andsolvent was evaporated under reduced pressure to afford crude product.The crude was purified by Isco silica gel flash column usingHexane-EtOAc (1:3) solvent system to afford pure acetic acid(S)-1-methyl-2-oxo-2-{4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethylester (2.3 g). ¹H NMR (CDCl₃) δ 7.79 (d, J=8.2 Hz, 2H), 7.36 (d, J=8.2Hz, 2H), 5.37 (d, J=6.6 Hz, 1H), 4.53 (t, J=14.0 Hz, 1H), 4.14-4.00 (m,2H), 3.78 (t, J=13.0 Hz, 1H), 3.10-2.92 (m, 1H), 2.60-2.40 (m, 4H), 2.12(s, 3H), 1.80-1.50 (m, 5H), 1.41 (d, J=6.6 Hz, 3H), 1.20-1.00 (m, 2H);LC-MS [M+H]⁺ 398.3.

Intermediates 122-151 were prepared using one of the methods describedfor intermediates 119-121 and are summarized in table 14. TABLE 14Intermediate Structure Name and Analytical data 122

Toluene-4-sulfonic acid 2-[1-((R)-2-tert-butoxycarbonylamino-propionyl)- piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 455.2 123

Toluene-4-sulfonic acid 2-[1-((S)-2- tert-butoxycarbonylamino-3-methyl-butyry)-piperidin-3-yl]-ethyl ester. LC- MS[M + H]⁺ 483.3 124

Toluene-4-sulfonic acid 2-[1-((S)-2- tert-butoxycarbonylamino-4-methyl-pentanoyl)-piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 497.3 125

Toluene-4-sulfonic acid 2-[1-((R)-2-tert-butoxycarbonylamino-propionyl)- piperidin-3-yl]-ethyl ester. LC-MS[M + H]⁺ 455.2 126

Toluene-4-sulfonic acid 2-[1-((S)-2-tert-butoxycarbonylamino-propionyl)- piperidin-3-yl]-ethyl ester. LC-MS[M + H]⁺ 455.2 127

Toluene-4-sulfonic acid 2-[1-(2-tert-butoxycarbonylamino-acetyl)-piperidin- 4-yl]-ethyl ester. LC-MS[M + H]⁺441.3 128

Toluene-4-sulfonic acid 2-[1-(2- dimethylamino-acetyl)-piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 369.2 129

Toluene-4-sulfonic acid 2-[1-(1-tert- butoxycarbonylamino- cyclopropanecarbonyl)-piperidin-4-yl]- ethyl ester. LC-MS[M + H]⁺ 467.4 130

Toluene-4-sulfonic acid 2-[1-(2-tert- butoxycarbonylamino-2-methyl-propionyl)-piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 469.3 131

Toluene-4-sulfonic acid 2-[1-((S)-2- tert-butoxycarbonylamino-3-methyl-butyry)-piperidin-4-yl]-ethyl ester. LC- MS[M + H]⁺ 483.2 132

Toluene-4-sulfonic acid 2-{1[(S)-2- (tert-butoxycarbonyl-methyl-amino)-propionyl]-piperidin-4-yl}-ethyl ester. LC-MS[M + H]⁺ 469.2 133

Toluene-4-sulfonic acid 2-{1[(R)-2- (tert-butoxycarbonyl-methyl-amino)-propionyl]-piperidin-4-yl}-ethyl ester. LC-MS[M + H]⁺ 469.3 134

Toluene-4-sulfonic acid 2-[1-((S)-2- tert-butoxycarbonylamino-4-methyl-pentanoyl)-piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 497.4 135

Toluene-4-sulfonic acid 2-[1-((S)-2-acetylamino-propionyl)-piperidin-4-yl]- ethyl ester. LC-MS[M + H]⁺ 397.1136

Toluene-4-sulfonic acid 2-[1-(2,2- dimethyl-[1,3]dioxolane-4-carbonyl)-piperidin-4-yl]-ethyl ester. LC-MS [M + H]⁺ 412.2 137

Toluene-4-sulfonic acid 2-[1-(2- methoxy-acetyl)-piperidin-4-yl]-ethylester. LC-MS[M + H]⁺ 356.1 138

Toluene-4-sulfonic acid 2-[1-((S)-2- methoxy-propionyl)-piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 370.2 139

Toluene-4-sulfonic acid 2-[1-((R)-2- methoxy-propionyl)-piperidin-4-yl]-ethyl ester. LC-MS[M + H]⁺ 370.2 140

Acetic acid(S)-1-methyl-2-oxo-2-{4-[2- (toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethyl ester. LC-MS [M + H]⁺ 398.3 141

Acetic acid 2-oxo-2-{4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidin-l-yl}- ethyl ester LC-MS[M + H]⁺ 384.2 142

(S)-2-{4-[2-(Toluene-4-sulfonyloxy)-ethyl]-piperidine-1-carbonyl}-azetidine- 1carboxylic acid tert-butylester. NMR(CDCl₃) δ 7.79(d, J=8.4 Hz, 2H), 7.36(d, J=8.4 Hz, 2H),4.90(m, 1H), 4.57(m, 1H), 4.10-3.98(m, 3H), 3.85(m, 1H), 3.68(m, 1H),2.97 and 2.89(td, J=13.2, 2.4 Hz, and J=14.0, 2.4 Hz, 1H), 2.51(m, 1H),2.46(s, 3H), 2.12(m, 1H), 1.73-1.56(m, 6H), 1.43 (s, 9H), 1.15-0.97(m,2H); 143

(S)-2-{4-[2-(Toluene-4-sulfonyloxy)- ethyl]-piperidine-1-carbonyl}-pyrrolidine-1 carboxylic acid tert-butyl ester. ¹H NMR(CDCl₃) δ 7.79(d,J=8.4 Hz, 2H), 7.36(d, J=8.4 Hz, 2H), 4.67-4.50(m, 2H), 4.10-4.05(m,2H), 3.86(m, 1H), 3.62-3.38(m, 2H), 3.04 and 2.93(brt, J=13.0 Hz, 1H),2.41(s, 3H), 2.40(m, 1H), 2.15(m, 1H), 2.09 (m, 1H), 1.88-1.76(m, 2H),1.71-1.52 (m, 5H), 1.45 and 1.39(s, 9H), 1.12- # 0.96(m, 2H) 144

(S)-2-{4-[2-(Toluene-4-sulfonyloxy)- ethyl]-piperidine-1-carbonyl}-piperidine-icarboxylic acid tert-butyl ester. ¹H NMR(CDCl₃) δ 7.79(brd,J=8.4 Hz, 2H), 7.36(brd, J=8.4 Hz, 2H), 5.01(m, 1H), 4.51(m, 1H),4.09-4.04 (m, 2H), 3.88-3.78(m, 2H), 3.27(m, 1H), 2.91(m, 1H), 2.46(s,3H), 2.42 (m, 1H), 1.82(m, 1H), 1.70-1.52(m, 10H), 1.44(s, 9H), 1.03(m,2H) 145

Toluene-4-sulfonic acid 2-[(S)-1-((R)-2-tert-butoxycarbonylamino-propionyl)- piperidin-3-yl]-ethyl ester. LC-MS[M + H]⁺ 455.2 146

Toluene-4-sulfonic acid 2-(1-{2-[2-(2- methoxy-ethoxy)-ethoxy]-acetyl}-piperidin-4-yl)-ethyl ester. LC-MS [M + H]⁺ 444.4 147

Toluene-4-sulfonic acid 2-{1-[2-(2- methoxy-ethoxy)-acetyl]-piperidin-4-yl)-ethyl ester. LC-MS[M + H]⁺ 400.2 148

Acetic acid 1,1-dimethyl-2-oxo-2-{4-[2- (toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethyl ester. LC-MS [M + H]⁺ 412.2 149

Toluene-4-sulfonic acid 2[(R)-1-((R)-2-tert-butoxycarbonylamino-propionyl)- piperidin-3-yl]-ethyl ester. LC-MS[M + H]⁺ 455.2 150

Toluene-4-sulfonic acid 1-((S)-2-tert- butoxycarbonylamino-propionyl)-piperidin-3-ylmethyl ester. LC-MS [M + H]⁺ 463.5 151

Toluene-4-sulfonic acid 1-((R)-2-tert- butoxycarbonylamino-propionyl)-piperidin-4-ylmethyl ester. LC-MS [M + H]⁺ 463.2

Examples 693 and 694[(S)-2-(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-piperidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamicacid tert-butyl ester and[(S)-2-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-piperidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamicacid tert-butyl ester.

Reagents: (a) Barton's base, DMF, 90-100° C.

A mixture of toluene-4-sulfonic acid2-[1-((S)-2-tert-butoxycarbonylamino-propionyl)-piperidin-4-yl]-ethylester (0.223 g, 0.49 mmol),8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine (0.075 g,0.20 mmol), and Barton's base (101 μL, 0.49 mmol) in DMF (2.5 mL) washeated at 90-100° C. for 15 h. After cooling, the reaction mixture wasconcentrated under reduced pressure. The residue was purified bypreparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobilephase: solvent A: Water HPLC grade containing 0.01% TFA, and solvent B:acetonitrile containing 0.01% TFA, general eluting gradient—solvent B15% to 80 over 15 to 25 minutes run time]. After lyophilization of HPLCfractions N-9 and N-3 isomers were isolated as trifluoroacetate salts.[(S)-2-(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-piperidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamicacid tert-butyl ester: ¹H NMR (CDCl₃) δ 8.20 (s, 1H), 7.15 (s, 1H), 7.06(s, 1H), 6.07 (s, 2H), 5.57 (d, J=7.8 Hz, 1H), 4.68-4.55 (m, 2H), 4.29(t, J=7.4 Hz, 2H), 3.96-3.85 (m, 1H), 1.98-1.75 (m, 4H), 1.66-1.5 (m,1H), 1.44 (s, 9H), 1.36-1.22 (m, 5H); TOF-MS [M+H]⁺ 648.16.{(S)-2-(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-piperidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamicacid tert-butyl ester, TOF-MS [M+H]⁺ 648.16.

Examples 695-741 were synthesized in the same manner as described forexamples 693 and 694 using appropriate starting materials and areisolated as a trifluoroacetate salts after preparative HPLCpurification. TABLE 15 Example Structure Name and analytical data 695

tert-Butyl{(1R)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-l-yl]-1- methyl-2-oxoethyl}carbamate. ¹HNMR (CDCl₃) δ 8.19(s, 1H), 7.16(s, 1H), 7.09(s, 1H), 6.08(s, 2H),5.57(d, J=7.8 Hz, 1H), 4.5-4.68(m, 2H), 4.3(t, J=7.4 Hz, 2H),3.85-3.96(m, 1H), 1.98-1.75(m, 4H), 1.66-1.50(m, 1H), 1.44 (s, 9H),1.36-1.22(m, 5H); TOF-MS [M + H]⁺ # 648.1 696

tert-Butyl{(1R)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1- methyl-2-oxoethyl}-carbamate.TOF- MS[M + H]⁺ 648.1 697

tert-Butyl((1S)-1-{[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}-2-methylpropyl)- carbamate. ¹H NMR(CDCl₃) δ 8.19(s, 1H),7.16(s, 1H), 7.11(s, 1H), 6.08(s, 2H), 5.40-5.32(m, 1H), 4.5-4.25(m,4H), 3.90-3.75(m, 1H), 3.25-3.05(m, 1H), 2.80-2.60(m, 1H), 2.10-1.65(m,4H), 1.65-1.25(m, 12H), 1.00-0.82(m, 6H); TOF-MS[M + H]⁺ # 676.1 698

tert-Butyl((1S)-1-{[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidin-1-yl]carbonyl}-2- methylpropyl)carbamate. TOF-MS [M + H]⁺ 676.1 699

tert-Butyl((1S)-1-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}-3-methylbutyl)carbamate. ¹H NMR(CDCl₃) δ 8.19(s, 1H), 7.16(s, 1H), 7.09(s, 1H), 6.08(s, 2H), 5.42-(t, J=6.6 Hz, 2H), 4.00-3.85(m,1H), 3.03(q, J=12.1 Hz, 1H), 2.57(q, J=12.5 Hz, 1H), 1.98-1.65(m, 6H),1.60-1.20(m, 13H), 1.02-0.90(m, 6H); TOF- MS[M + H]⁺ # 690.2 700

tert-Butyl((1S)-1-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidin-1-yl]carbonyl}-3-methylbutyl)carbamate. TOF-MS[M + H]⁺ 690.2 701

tert-Butyl{(1R)-2-[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1- methyl-2-oxoethyl}carbamate. ¹HNMR (CDCl₃) δ 8.19(s, 1H), 7.15(s, 1H), 7.10(s,1H), 6.08(s, 2H), 5.55(m,1H), 4.70-4.55(m, 1H), 4.38-4.25(m, 3H), 6.82-3.65(m, 1H), 3.20-3.05(m,1H), 2.85-2.70(m, 1H), 2.10-1.95(m, 1H), 1.95-1.65(m, 3H), 1.62-1.48(m,2H), 1.43(s,9H), 1.29(d, J= # 7.0 Hz, 3H); LC-MS[M + H]⁺ 648.1 702

tert-Butyl{(1R)-2-[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1- methyl-2-oxoethyl}carbamate.LC-MS [M + H]⁺ 648.1 703

tert-Butyl{(1S)-2-[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1- methyl-2-oxoethyl}carbamate.TOF-MS [M + H]⁺ 648.1 704

tert-Butyl{(1S)-2-[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1- methyl-2-oxoethyl}carbamate.TOF-MS [M + H]⁺ 648.1 705

tert-Butyl{2-[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2- oxoethyl}carbamate. ¹H NMR(CDCl₃) δ8.27(s, 1H), 7.11(s, 1H), 6.93(s, 1H), 6.03(s, 2H), 5.55(broad s, 1H),4.58(d, J=13.2 Hz, 1H), 4.27(t, J=7.4 Hz, 2H), 3.94(dq, J=3.9, 16.8 Hz,2H), 3.69(d, J=12.5 Hz, 1H), 2.95(t, J=11.3 Hz, 1H), 2.57(t, J=11.3 Hz,1H), 1.92-1.70(m, 4H), 1.60-1.48(m, # 1H), 1.44(s, 9H), 1.35-1.10(m,2H); TOF-MS[M + H]⁺ 634.1 706

tert-Butyl{2-[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-2- oxoethyl}carbamate. TOF-MS[M +H]^(+634.1) 707

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(dimethylamino)acetyl]piperidin-4- yl}ethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.26(s, 1H), 7.28(s, 1H), 7.16(s, 1H), 6.08(s, 2H),4.55-4.45(m, 1H), 4.35(t, J=7.8 Hz, 2H), 4.22(q, J=16.4 Hz, 2H),3.70-3.62(m, 1H), 3.12-3.01(m, 1H), 2.92(s, 6H), 2.74-2.65(m, 1H),1.96-1.75(m, 4H), 1.69-1.48(m, 1H), 1.25-1.10(m, 2H); TOF- MS[M + # H]⁺562.1 708

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-{1-[(dimethylamino)acetyl]piperidin-4- yl}ethyl)-3H-purin-6-amine. LC-MS[M + H]⁺ 562.8 709

tert-Butyl(1-{[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1- yl]carbonyl}cyclopropyl)carbamate. ¹HNMR(CDCl₃) δ 8.10(s, 1H), 7.17(s, 1H), 7.10(s, 1H), 6.09(s, 2H),5.35-5.25(m, 1H), 4.68-4.55(m, 1H), 4.30 (t, J=7.8 Hz, 2H), 2.86-2.7(m,2H), 1.87(d, J=13.2 Hz, 2H), 1.79(q, J=7.0 Hz, 2H), 1.65-1.50(m, 1H),1.42(s, 9H), 1.30-1.10(m, 6H); TOF-MS # [M + H]⁺ 660.1 710

tert-Butyl(1-{[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1- yl]carbonyl}cyclopropyl)carbamate.LC-MS[M + H]⁺ 660.1 711

tert-Butyl{2-[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-9H-dimethyl-2-oxoethyl}carbamate. NMR(CD₃OD) δ 8.19(s, 1H), 7.26(s, 1H),7.10(s, 1H), 6.07(s, 2H), 4.60-4.50(m, 1H), 4.36-4.28(m, 2H),3.50-3.46(m, 1 H), 3.10-3.00(m, 1H), 2.70-2.60(m, 1H), 1.85-1.71(m, 4H),1.64-1.52(m, 1H), 1.46-1.38(m, 15 H), 1.28-1.10(m, 2H); TOF-MS[M +H]^(+662.1) 712

tert-Butyl{2-[4-(2-{6-amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1,1- dimethyl-2-oxoethyl}carbamate. LC-MS[M + H]⁺ 662.1 713

tert-Butyl((1S)-1-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}-2- methylpropyl)carbamate. ¹H NMR (CD₃OD) δ 8.30(s, 1H),7.28(s, 1H), 7.18(d, J=5.86 Hz, 1H), 6.08(s, 2H), 4.55-4.44(m, 1H),4.40-4.32(m, 3H), 4.58-4.06(m, 1H), 3.15-3.05(m, 1H), 2.69-2.59(m, 1H),2.00-1.72(m, 5H), 1.68-1.56(m, 1H), 1.43(d, J=3.9 Hz, 6 H), 1.28(s, 9H), # 1.20-1.06(m, 2H); TOF-MS[M + H]⁺ 676.1 714

tert-Butyl((1S)-1-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidin-1-yl]carbonyl}-2- methylpropyl)carbamate. LC-MS [M + H]⁺ 676.1 715

tert-Butyl{(1S)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}methylcarbamate. ¹H NMR(CDCl₃) δ 8.19(s, 1H), 7.17 (s,1H), 7.10(s, 1H), 6.09(s, 2H), 5.15-5.05(m, 1H), 4.70-4.50(m, 1H),4.35-4.25(m, 2H), 4.10-4.00(m, 1H), 3.00-2.80(m, 1H), 2.74(s, 3H),2.60-2.45 (m, 1H), 1.90-1.68(m, 4H), 1.70-1.45 (m, 10H), 1.30-1.00(m, #5 H), TOF-MS [M + H]⁺ 662.1 716

tert-Butyl{(1S)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}methylcarbamate. LC-MS[M + H]⁺ 662.1 717

tert-Butyl{(1R)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}methylcarbamate, ¹H NMR(CD₃OD) δ 8.28(s, 1H), 7.27 (s,1H), 7.20-7.14(m, 1H), 6.08(s, 2H), 5.10-4.99(m, 1H), 4.51(d, J=11.3 Hz,1H), 4.50-4.30(m, 2H), 4.00-3.88(m, 1H), 3.05-2.96(m, 1H), 2.78-2.55(m,4H), 1.95-1.70(m, 4H), 1.70-1.55(m, 1H), 1.46(s, 9H), 1.20- # 1.00(m, 5H); TOF-MS[M + H]⁺ 662.1 718

tert-Butyl{(1R)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}methylcarbamate, LC-MS[M + H]⁺ 662.1 719

tert-Butyl((1S)-1-{[3-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}-3-methylbutyl)carbamate, ¹H NMR(CDCl₃) δ 8.23(s, 1H),7.80-7.15(m, 1H), 7.13-7.10(m, 1H), 6.73-6.62(broad s, 1H), 6.09(s, 2H),5.48-5.35(m, 1H), 4.70-4.60(m, 1H), 4.40-4.10(m, 3H), 3.90-3.70(m, 1H),3.30-3.00(m, 1H), 2.90-2.60(m, 1H), 2.10-1.20(m, 24H); TOF- # MS[M + H]⁺690.2 720

N-{(1S)-2-[4-(2-{6-amino-8-[(6-bromo- 1,3-benzodioxol-5-yl)thio]-9H-purin-9- yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}acetamide. LC-MS[M + H]^(+590.1) 721

N-{(1S)-2-[4-(2-{6-Amino-8-[(6- bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1- methyl-2-oxoethyl}acetamide. LC-MS[M + H]⁺ 590.1 722

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-{2-[1-(methoxyacetyl)piperidin-4-yl]ethyl}- 9H-purin-6-amine. ¹H NMR(CD₃OD)δ8.29(s, 1H), 7.28(s, 1H), 7.18(s, 1H), 6.08(s, 2H), 4.47(d, J=12.8 Hz,1H), 4.36(t, J=7.42 Hz, 2H), 4.13(q, J=14.0 Hz, 2H), 3.83(d, J=13.6 Hz,1H), 3.38(s, 3H), 3.00(dt, J=2.3, 13.28 Hz, 1H), 2.61(dt, J=2.7, 12.8Hz, 1H), 1.87(d, J=12.0 Hz, 2H), 1.81(q, J=7.0 Hz, 2H), 1.65- # 1.52(m,1H), 1.3-1.10(m, 2H); TOF-MS[M + H]⁺ 549.0 723

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-{2-[1-(methoxyacetyl)piperidin-4-yl]ethyl}- 3H-purin-6-amine. TOF-MS[M +H]^(+549.0) 724

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(2S)-2-methoxypropanoyl]piperidin-4- yl}ethyl)-9H-purin-6-amine. ¹H NMR (CDCl₃)δ 8.31(s, 1H), 7.10(s, 1H), 6.87(s, 1H), 6.30-5.90(broad peak withsinglet at 6.01, 3H), 4.65-4.56(m, 1H), 4.27(t, J=7.42 Hz, 2H),4.22-4.10(m, 2H), 3.33(d, J=7.8 Hz, 3H), 3.00-2.88 (m, 1H), 2.60-2.50(m,1H), 1.85(d, J=12.5 Hz, 2H), 1.74(q, J=6.2 Hz, 2H), # 1.60-1.47(m, 1H),1.38(d, J=6.6 Hz, 3H), 1.30-1.10(m, 2H); TOF-MS [M + H]⁺ 563.11 725

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(2R)-2-methoxypropanoyl]piperidin-4- yl}ethyl)-9H-purin-6-amine. ¹H NMR (CDCl₃)δ 8.22(s, 1H), 7.14(s, 1H), 7.03(s, 1H), 6.06(s, 2H), 4.65-4.56(m, 1H),4.27(t, J=7.42 Hz, 2H), 4.22-4.10(m, 2H), 3.33(d, J=7.8 Hz, 3H),3.00-2.88(m, 1H), 2.60-2.50(m, 1H), 1.85(d, J=12.5 Hz, 2H), 1.74(q,J=6.2 Hz, 2H), 1.60-1.47(m, 1H), 1.38(d, J=6.6 # Hz, 3H), 1.30-1.10(m,2H); TOF-MS[M + H]⁺ 563.1 726

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-{1-[(2R)-2-methoxypropanoyl]piperidin-4- yl}ethyl)-3 H-purin-6-amine. ¹H NMR(CDCl₃) δ 10.71(s, 1H), 8.06(s, 1H), 7.21(s, 1H), 7.18(s, 1H), 6.17(s,1H), 6.11(s, 2H), 4.65-4.55(m, 1H), 4.40-4.30(m, 2H), 4.30-4.10(m, 2H),3.35 (d, J=8.5 Hz, 3H), 3.02-2.9(m, 1H), 2.60-2.50(m, 1H), 1.89(q, J=7.0Hz, 2H), 1.85-1.75(m, 2H), 1.60-1.47(m, 1H), 1.39(d, # J=6.6 Hz, 3H),1.30-1.10 (m, 2H); TOF-MS[M + H]⁺ 563.1 727

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-(2-{1-[(2S)-2-methoxypropanoyl]piperidin-4- yl}ethyl)-3 H-purin-6-amine. ¹H NMR(CDCl₃) δ 10.62(s, 1H), 8.07(s, 1H), 7.21(s, 1H), 7.18(s, 1H), 6.11(s,2H), 4.65-4.55(m, 1H), 4.40-4.30(m, 2H), 4.30-4.10(m, 2H), 3.35(d, J=8.5Hz, 3H), 3.02-2.90(m, 1H), 2.60-2.50(m, 1H), 1.89(q, J=7.0 Hz, 2H),1.85-1.75 (m, 2H), 1.60-1.47(m, 1H), 1.39(d, J= # 6.6 Hz, 3H),1.30-1.10(m, 2H); TOF- MS[M + H]⁺ 563.1 728

tert-Butyl(2S)-2-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}azetidine-1-carboxylate. ¹H NMR(CD₃OD) δ 8.27(s, 1H),7.28(s, 1H), 7.17 and 7.15(s, 1H), 6.09(s, 2H), 5.05(m, 1H), 4.48(m,1H), 4.36(t, J=6.0 Hz, 2H), 3.93-3.87(m, 2H), 3.76 (m, 1H), 3.02(m, 1H),2.66(m, 1H), 2.56(m, 1H), 1.42(s, 9H), 2.07(m, 1H), 1.87-1.77(m, 5H),1.62(m, 1H), # 1.17(m, 1H); LC-MS[M + H]⁺ 660.1 729

tert-Butyl(2S)-2-{[4-(2-{6-amino-8- [(6-bromo-1,3-ethyl)piperidin-1-1,3-benzodioxol-5-yl)thio]- yl]carbonyl}azetidine-1-carboxylate,LC-MS[M + H]⁺ 660.1 730

tert-Butyl(2S)-2-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}pyrrolidine-1-carboxylate, ¹H NMR(CD₃OD) δ 8.30 and 8.29(s,1H), 7.29 and 7.286(s, 1H), 7.20, 7.19, and 7.18(s, 1H), 6.09(s, 2H),4.69(m, 1H), 4.49(m, 1H), 4.39-4.34(m, 2H), 4.02(m, 1H), 3.53-3.42(m,2H), 3.06 (m, 1H), 2.62(m, 1H), 2.26(m, 1H), 1.89-1.78(m, 7H), 1.62(m,1H), 1.46, 1.45, # 1.42, and 1.37(s, 9H), 1.32-1.15 (m, 2H); LC-MS[M +H]⁺ 674.2 731

tert-Butyl(2S)-2-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidin-1-yl]carbonyl}pyrrolidine-1-carboxylate, ¹H NMR(CD₃OD) δ 8.55, 8.54, and8.535(s, 1H), 7.40,-7.37(m, 2H), 6.17 and 6.16(s, 2H), 4.69(m, 1H),4.48(m, 1H), 4.43(t, J=7.2 Hz, 2H), 4.01(m, 1H), 3.54-3.41(m, 2H),3.06(m, 1H), 2.64(m, 1H), 2.28(m, 1H), 1.89-1.78 (m, 7H), 1.62(m, 1H),1.47, 1.46, 1.43, # and 1.38(s, 9H), 1.19(m, 2H); LC-MS [M + H]⁺ 674.2732

tert-Butyl(2S)-2-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 9H-purin-9-yl}ethyl)piperidin-1-yl]carbonyl}piperidine-1-carboxylate, ¹H NMR(CD₃OD) δ 8.30(s, 1H), 7.29(s, 1H), 7.20(s, 1H), 6.09(s, 2H), 4.47 (m, 1H), 4.37(t, J==7.2 Hz, 2H),3.97-3.84(m, 2H), 3.31-3.29(m, 1H), 3.25 (m, 2H), 3.06(m, 1H), 2.59(m,1H), 1.96-1.78(m, 7H), 1.74-1.58(m, 4H), 1.45(s, 9H), 1.18(m, 1H); LC-MS# [M + H]⁺ 688.2 733

tert-Butyl(2S)-2-{[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]- 3H-purin-3-yl}ethyl)piperidin-1-yl]carbonyl}piperidine-1- carboxylate. LC-MS[M + H]⁺ 688.2 734

tert-Butyl{(1R)-2-[(3S)-3-(2-{6-amino- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate, ¹H NMR 6(CD₃OD), 8.18(s, 1H),7.30(s, 1H), 7.10(s, 1H), 6.10(s, 2H), 4.30-4.20(m, 2H), 3.60-3.50(m,2H), 3.20-3.14(m, 2H), 3.10(m, 2H), 2.80-2.70(m, 2H), 2.40(m, 2H),1.60-1.50 (m, 2H), 1.43(s, 9H), 1.40(s, 3H). LC- MS[M + H]⁺ 648.2 735

tert-Butyl{(1R)-2-[(3S)-3-(2-{6-amino- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3 H-purin-3-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate, LC-MS[M + H]⁺ 648.2 736

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-{[2-(2-methoxyethoxy)-ethoxy]-acetyl}-piperidin-4-yl)-ethyl]- 9H-purin-6-amine. LC-MS[M +H]^(+637.4) 737

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-3-[2-(1-{[2-(2-methoxyethoxy)-ethoxy]-acetyl}-piperidin-4-yl)-ethyl]- 3H-purin-6-amine. LC-MS[M +H]^(+637.4) 738

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(2-methoxyethoxy)-acetyl]-piperidin-4-yl}-ethyl)-9H-purin- 6-amine. LC-MS[M + H]⁺ 593.1739

8-[(6-Bromo-1,3-benzodioxol-5-yl)- thio]-3-(2-{1-[(2-methoxyethoxy)-acetyl]-piperidin-4-yl}-ethyl)-3 H-purin- 6-amine. LC-MS[M + H]⁺ 593.4740

tert-Butyl{(1R)-2-[(3R)-3-(2-{6-amino- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate, LC-MS IIM + H]⁺ 649.3 741

tert-Butyl{(1R)-2-[(3R)-3-(2-{6-amino- 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate, LC-MS[M + H]⁺ 649.3

Example 7429-(2-{1-[(2S)-2-Aminopropanoyl]piperidin-4-yl}ethyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine

Reagent: (a) TFA, DCM.

To a solution of[(S)-2-(4-{2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-piperidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamicacid tert-butyl ester (0.014 g, 0.021 mmol) in DCM (3 mL) was added dropwise TFA (100 μL) and the resulting mixture was stirred for overnight atroom temperature. After concentration under reduced pressure, theresidual TFA was removed to afford a title product (0.015 g) as a TFAsalt. ¹H NMR (CD₃OD) δ 8.34 (s, 1H), 7.28 (s, 1H), 7.23 (s, 1H), 6.09(s, 2H), 4.54-4.44 (m, 2H), 4.39 (t, J=7.42 Hz, 2H), 3.85 (broad d,J=13.2 Hz, 1H), 3.19-3.08 (m, 1H), 2.75-2.63 (m, 1H), 2.00-1.80 (m, 4H),1.70-1.58 (m, 1H), 1.44 (dd, J=14.8, 7.0 Hz, 3H), 1.35-1.13 (m, 2H);LC-MS [M+H]⁺ 548.2

The examples 743-755 are summarized in table 16, were synthesized in thesame manner as described for example 742 using appropriate startingmaterials and are isolated as a trifluoroacetate salt. TABLE 16 Ex- am-ple Structure Name and analytical data 743

9-(2-{1-[(2R)-2- Aminopropanoyl]piperidin-3- yl}ethyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹H NMR (CD₃OD) δ 8.30 (s, 1H), 7.28 (s, 1 H), 7.23 (s, 1 H), 6.09 (s, 2 H), 4.50- 4.20 (m, 4 H),4.30-4.18 (m, 1 H), 3.80-3.65 (m, 1 H), 3.20- 3.10 (m, 1 H), 2.78-2.65(m, 1 H), 2.10-2.00 # (m, 1 H), 2.00- 1.75 (m, 3 H), 1.60-1.30 (m, 5 H);LC-MS [M + H]⁺ 548.1 744

9-(2-{1-[(2S)-2-Amino-4- methylpentanoyl]piperidin-4-yl}ethyl)-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹HNMR (CD₃OD) δ 8.34 (s, 1 H), 7.28 (s, 1 H), 7.22 (s, 1 H), 6.09 (s, 2H), 4.58-4.28 (m, 4 H), 3.79 (broad d, J = 13.2 Hz, 1 H), 3.13 (t, J =12.8 Hz, 1 H), 2.76-2.62 (m, 1H), # 2.00-1.50 (m, 7 H), 1.35-1.10 (m, 3H), 1.08-0.95 (m, 6 H); LC-MS [M + H]⁺ 590.1 745

9-(2-{1-[(2S)-2-Amino-3- methylbutanoyl]piperidin-3-yl}ethyl)-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H- purin-6-amine.TOF-MS [M + H]⁺ 576.1 746

9-(2-{1-[(2R)-2- Aminopropanoyl]piperidin-4- yl}ethyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹H NMR (CD₃OD) δ 8.34 (s, 1H), 7.28 (s, 1 H), 7.23 (s, 1 H), 6.09 (s, 2 H), 4.54-4.44 (m, 2 H),4.39 (t, J = 7.42 Hz, 2 H), 3.85 (broad d, J = 13.2 Hz, 1 H), 3.19-3.08(m, 1 H), # 2.75-2.63 (m, 1 H), 2.00-1.80 (m, 4 H), 1.70-1.58 (m, 1 H),1.44 (dd, J = 14.8, 7.0 Hz, 3 H), 1.35-1.13 (m, 2 H); LC-MS [M + H]⁺548.2 747

9-(2-{1-[(2S)-2- Aminopropanoyl]piperidin-3- yl}ethyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹H NMR (CD₃OD) δ 8.34 (s, 1H), 7.28 (s, 1 H), 7.24 (s, 1 H), 6.10 (s, 2 H), 4.50-4.35 (m, 3 H),4.30-4.20 (m, 1 H), 3.78-3.68 (m, 1 H), 3.24-3.16 (m, 1 H), 2.72 (dd, J=10.1, 12.8 Hz, 1 H), # 2.10-2.00 (m, 1 H), 2.00-1.75 (m, 3 H),1.60-1.30 (m, 6 H); LC-MS [M + H]⁺ 548.1 748

9-(2-{1-[(2S)-2-Amino-4- methylpentanoyl]piperidin-3-yl}ethyl)-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹HNMR (CD₃OD) δ 8.38-8.32 (m, 1 H), 7.28 (s, 1 H), 7.25-7.20 (m, 1 H),6.10 (s, 2 H), 4.60- 4.20 (m, 4 H), 3.70-3.60 (m, 1 H), 3.45-3.15 (m, 1H), 3.00- 2.65 (m, 2 H), 2.30-1.20 (m, # 15 H); LC-MS [M + H]⁺ 590.2 749

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(2S)-2-(methylamino)propanoyl]piperidin-4-yl}ethyl)-9H-purin- 6-amine. ¹H NMR(CD₃OD) δ 8.34 (s, 1 H), 7.29 (s, 1 H), 7.23 (s, 1 H), 6.09 (s, 2 H),4.50 (d, J = 13.2 Hz, 1 H), 4.30-4.44 (m, 2 H), 3.83 (d, J = 14.8 Hz, 1H), 3.08- 3.20 (m, # 2 H), 2.62-2.76 (m, 4 H), 1.80-2.00 (m, 4 H),1.55-1.70 (m, 1 H), 1.46 (dd, J = 15.6, 7.0 Hz, 3 H), 1.35-1.10 (m, 2H); LC-MS [M + H]⁺ 562.1 750

9-{2-[1-(2-Amino-2- methylpropanoyl)piperidin-4-yl]ethyl}-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹HNMR (CD₃OD) δ 8.34 (s, 1 H), 7.28 (s, 1 H), 7.22 (s, 1 H), 6.09 (s, 2H), 4.45-4.16 (m, 4 H), 3.10-2.80 (m, 2 H), 1.94 (d, J = 12.8 Hz, 2 H),1.84 (q, J = 7.0 Hz, # 2 H), 1.66 (s, 7 H), 1.32-1.15 (m, 2 H); TOF-MS[M + H]⁺ 562.0 751

9-(2-{1-[(1-Amino- cyclopropyl)carbonyl]piperidine-4-yl}ethyl)-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H- purin-6-amine.¹H NMR (CD₃OD) δ 8.27 (s, 1 H), 7.28 (s, 1 H), 7.18 (s, 1 H), 6.09 (s, 2H), 4.36 (t, J = 7.42 Hz, 2 H), 4.28 (d, J = 12.8 Hz, 2 H), 2.95 (t, J =12.1 Hz, 2 H), 1.92 # (d, J = 11.3 Hz, 2 H), 1.83 (q, J = 7.03 Hz, 2 H),1.70-1.58 (m, 1 H), 1.39- 1.33 (m, 2 H), 1.32-1.21 (m, 4 H); TOF-MS [M +H]⁺ 560.1 752

9-(2-{1-[(2S)-Azetidin-2-ylcarbonyl]piperidin-4-yl}ethyl)-8-[(6-bromo-1,3-benzo-dioxol-5-yl)thio]-9H-purin- 6-amine. ¹H NMR (CD₃OD) δ 8.30 (s, 1 H),7.29 (s, 1 H), 7.20 and 7.19 (two s, 1 H), 6.09 (s, 2 H), 5.36 (m, 1 H),4.48 (m, 1 H), 4.37 (t, J = 7.6 Hz, 2 H), 4.11 (m, 1 H), 3.90 (m, 1 H),# 3.41 (m, 1 H), 3.30 (m, 1 H), 2.89 (m, 1 H), 2.75 (m, 1 H), 2.56 (m, 1H), 1.96- 1.88 (m, 3 H), 1.86-1.81 (m, 2 H), 1.33-1.19 (m, 2 H); LC-MS[M + H]⁺ 560.1 753

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-[2-(1-L-prolyl-piperidin-4-yl)ethyl]-9H- purin-6-amine. ¹H NMR (CD₃OD) δ 8.31 (s, 1 H),7.29 (s, 1 H), 7.21 and 7.20 (s, 1 H), 6.09 (s, 2 H), 4.66 and 4.62 (t,J = 8.4 and 7.2 Hz, 1 H), 4.59 (m, 1 H), 4.38 (t, J = 8.0 Hz, 2 H), 3.87(m, 1 H), 3.43-3.38 # (m, 1 H), 3.16-3.10 (m, 2 H), 2.73 (m, 1 H), 2.49(m, 1 H), 2.10-1.82 (m, 8 H), 1.65 (m, 1 H), 1.30-1.16 (m, 4 H), 0.88(m, 1 H); LC-MS [M + H]⁺ 574.1 754

8-[(6-Bromo-1,3-benzodioxol-5- yl)thio]-9-(2-{1-[(2S)-piperidin-2-ylcarbonyl]piperidin- 4-yl}ethyl)-9H-purin-6-amine. ¹H NMR(CD₃OD) δ 8.31 (s, 1 H), 7.29 (s, 1 H), 7.21 (s, 1 H), 6.10 (s, 2 H),4.48 (m, 1 H), 4.38 (t, J = 7.2 Hz, 2 H), 4.29 (m, 1 H), 3.84 (brd, J =13.6 Hz, 1 H), 3.41- 3.38 # (m, 2 H), 3.15-3.00 (m, 2 H), 2.68 (m, 1 H),2.10 (m, 1 H), 1.94-1.81 (m, 6 H), 1.76- 1.60 (m, 4 H), 1.28-1.12 (m, 1H); LC-MS [M + H]⁺ 588.1 755

9-(2-{(3S)-1-[(2R)-2- Aminopropanoyl]piperidin-3-yl}ethyl)-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H- purin-6-amine. ¹HNMR (CD₃OD) δ 8.20 (s, 1 H), 7.30 (s, 1 H), 7.20 (s, 1 H), 6.10 (s, 2H), 4.30-4.20 (m, 2 H), 3.50-3.40 (m, 2 H), 3.20-3.10 (m, 2 H),2.90-2.80 (m, 2 H), 2.40-2.30 (m, 2 H), 2.10-2.00 # (m, 2 H), 1.60-1.50(m, 2 H), 1.40 (s, 3 H); LC-MS [M + H]⁺ 548.2

Examples 756 and 757(2S)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-oland(2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol

Reagents: (a) Barton's base, DMF, 90-100° C.; (b) LiOH.H₂O, MeOH-THF—H₂O(1:1:1).

Step 1:

The alkylation reaction was carried out according to the proceduredescribed for example 1 and 2 using8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine (0.200 g,0.54 mmol) and acetic acid(S)-1-methyl-2-oxo-2-{4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethylester (0.325 g, 0.81 mmol) to afford mixture of N-3 and N-9 isomers.(1S)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethylacetate, LC-MS [M+H]⁺ 591.1 and(1S)-2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethylacetate, LC-MS [M+H]⁺ 591.1. The crude mixture was used in the nexthydrolysis reaction without further purification.

Step 2:

To a solution of above product in mixture of MeOH-THF—H₂O (1:1:1, 10 mL)was added LiOH.H₂O (0.1 g) and the resulting mixture was stirred forovernight at room temperature. After concentration of reaction mixtureunder reduced pressure, the residue was subjected to purification bypreparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobilephase: solvent A: Water HPLC grade containing 0.01% TFA, and solvent B:acetonitrile containing 0.01% TFA, general eluting gradient—solvent B15% to 80 over 15 to 25 minutes run time]. After lyophilization of HPLCfractions the title compounds were isolated as trifluoro acetate salt.(2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol.TOF-MS [M+H]⁺ 549.1 and(2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol,¹H NMR (CD₃OD) δ 8.31 (s, 1H), 7.28 (s, 1H), 7.20 (s, 1H), 6.09 (s, 2H),4.60-4.45 (m, 2H), 4.37 (t, J=7.8 Hz, 2H), 4.00 (d, J=12.0 Hz, 1H),3.10-2.98 (m, 1H), 2.70-2.56 (m, 1H), 1.96-1.79 (m, 4H), 1.70-1.55 (m,1H), 1.30 (dd, J=7.0, 10.1 Hz, 3H), 1.26-1.10 (m, 2H); LC-MS [M+H]⁺549.1

Examples 758-765 Examples 758-765 are prepared according to theprocedure described for examples 756 and 757 using appropriate startingmaterials. All the compounds summarized in the table 17 are isolated asa trifluoroacetate salt after HPLC purification.

TABLE 17 Example Structure Name and analytical data 758

2-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-oxoethyl acetate. LC-MS [M + H]⁺ 577.1 759

2-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-2-oxoethyl acetate LC-MS [M + H]⁺ 577.1 760

2-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-oxoethanol. ¹H NMR (DMSO-D₆) δ 8.20 (s, 1 H),7.74- 7.58 (broad s, 1 H), 7.39 (s, 1 H), 6.84 (s, 1 H), 6.09 (s, 2 H),4.29 (d, J = 12.5 Hz, 1 H), 4.19 (t, J = 7.4 Hz, 2 H), 4.00 (d, J =7.0Hz, 2 H), 3.60 (d, J = 13.6 Hz, 1 H), # 2.82 (t, J = 11.7 Hz, 1 H),2.56-2.44 (m, merged with solvent peak, 1 H), 1.70 (d, J = 11.7 Hz, 2H), 1.61 (q, J = 7.0 Hz, 2 H), 1.49-1.36 (m, 1 H), 1.12-0.90 (m, 2 H);TOF-MS [M + H]⁺ 535.06 761

2-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-2-oxoethanol. LC-MS [M + H]⁺ 535.1 762

2-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1,1-dimethyl-2- oxoethyl acetate. LC-MS [M +H]⁺ 605.1 763

2-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1,1-dimethyl-2- oxoethyl acetate. LC-MS [M +H]⁺ 605.1 764

1-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-methyl-1- oxopropan-2-ol. LC-MS [M + H]⁺563.1 765

1-[4-(2-{6-Amino-8-[(6-bromo-1,3- benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-2-methyl-1- oxopropan-2-ol. LC-MS [M + H]⁺563.1

Examples 766 and 767(2R)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-oland(2R)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol

Reagents: (a) TBDPS-Cl, Et₃N, THF, (b) LiOH.H₂O, MeOH, THF, H₂O, (c)(COCl)₂, DCM, cat. DMF, (d) 4-piperidine ethanol, Et₃N, THF, (e) p-TsCl,Et₃N, cat. DMAP, THF, (f) intermediate 34, Barton's base, DMF, 90-100°C., (g) TBAF, THF.

Step 1: (2R)-2-{[tert-Butyl(diphenyl)silyl]oxy}propanoic acid

To the mixture of (R)-2-Hydroxy-propionic acid methyl ester (1.0 g, 9.6mmol), triethyl amine (4.0 mL, 28.81 mmol) in tetrahydrofuran (12 mL),was added tert-butyldiphenylsilylchloride (3.68 mL, 14.4 mmol) at roomtemperature and allowed the reaction mixture to stir for 12 h. Aftercompletion of the reaction, the reaction mixture was diluted with EtOAc(80 mL) and washed with water (70 mL) and brine (70 mL). The EtOAc layerwas dried over Na₂SO₄ and solvent was evaporated in vacuo to affordmethyl (2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propanoate (3.28 g). Theabove crude material was sufficiently pure for the next step and usedwithout further purification. The crude material was diluted withTHF-MeOH—H₂O (1:1:1, 20 mL) and added LiOH. H₂O (1.17 g, 28.0 mmol). Thereaction mixture was stirred for over night at room temperature. Thereaction mixture neutralized with conc. HCl and concentrated in vacuo.The residue was diluted with 75 mL water and extracted with EtOAc (3×50mL), the combined EtOAc layers were dried over Na₂SO₄ and evaporated invacuo. The crude carboxylic acid was purified by Isco silica gel flashcolumn using EtOAc to obtain the carboxylic acid (0.6 g). ¹H NMR (CDCl₃)δ 7.70-7.60 (m, 4H), 7.50-7.38 (m, 6H), 4.32 (q, J=6.6 Hz, 1H), 1.30 (d,J=7.0 Hz, 9H); LC-MS [M−H]⁺ 327.2

Step 2:2-[1-((2R)-2-{[tert-Butyl-(diphenyl)silyl]-oxy}propanoyl)-piperidin-4-yl]-ethanol

To above carboxylic acid (0.6 g, 1.82 mmol) in dichloromethane (15 mL),oxalyl chloride (464 μL, 3.65 mmol) was added at ice cold temperaturefollowed by two drops of N,N-dimethyl formamide. The reaction mixturewas brought to room temperature and stirred for 6 h. At the end of thisperiod excess oxalyl chloride was evaporated under reduced pressure togive the corresponding acid chloride. The acid chloride was diluted with2 mL THF and added to a mixture of 4-piperidine ethanol (0.235 g, 1.8mmol), triethyl amine (763 μL, 5.48 mmol) in THF (7 mL) at roomtemperature. The reaction mixture was stirred for over night, aftercompletion of reaction the reaction mixture was diluted with EtOAc (60mL) and washed with sat. aq. NaHCO₃ solution (60 mL) and brine (60 mL).The EtOAc layer was dried over Na₂SO₄, filtered, and solvent wasevaporated under reduced pressure to afford crude product. The crude waspurified by Isco silica gel flash column using Hexane-EtOAc (1:3) togive 0.748 g of2-[1-((2R)-2-{[tert-butyl-(diphenyl)silyl]-oxy}propanoyl)-piperidin-4-yl]-ethanol.¹H NMR (CDCl₃) δ 7.70-7.60 (m, 4H), 7.46-7.33 (m, 6H), 4.55 (t, J=5.4Hz, 1H), 4.43 (d, J=12.8 Hz, 1H), 4.26 and 4.06 (2 d, J=12.5 Hz, 1H),3.66 (q, J=5.8 Hz, 2H), 2.86 and 2.69 (2 t, J=12.8 Hz, 1H), 2.5-2.34 (m,1H), 1.70-1.54 (m, 4H), 1.43 (q, J=6.6 Hz, 2H), 1.34 (t, J=7.0 Hz, 3H),1.20-1.28 (m, 1H), 1.08 (s, 9H); LC-MS [M+H]⁺ 440.3

Step 3:2-[1-((2R)-2-{[tert-Butyl-(diphenyl)-silyl]-oxy}-propanoyl)-piperidin-4-yl]-ethyl4-methylbenzenesulfonate

To the solution of2-[1-((2R)-2-{[tert-butyl-(diphenyl)silyl]-oxy}propanoyl)-piperidin-4-yl]-ethanol(0.748 g, 1.7 mmol) in tetrahydrofuran (10 mL) and added triethyl amine(711 μL, 5.11 mmol), N,N-dimethylpyridine (10 mg) followed by p-TsCl(0.487 g, 2.55 mmol) at room temperature and stirred the reactionmixture for 12 h. The reaction mixture was concentrated under vacuum anddiluted with EtOAc (60 mL), washed with sat. aq. NaHCO₃ solution (50 mL)and brine (50 mL). The EtOAc layer was dried over Na₂SO₄, filtered, andsolvent was evaporated under reduced pressure to afford crude product.The crude was purified by Isco silica gel flash column usingHexane-EtOAc (1:3) to give 0.69 g of2-[1-((2R)-2-{[tert-butyl-(diphenyl)-silyl]-oxy}-propanoyl)-piperidin-4-yl]-ethyl4-methylbenzenesulfonate. ¹H NMR (CDCl₃) δ 7.79 (d, J=7.8 Hz, 2H),7.68-7.58 (m, 4H), 7.40-7.32 (m, 8H), 4.60-4.50 (m, 1H), 4.44-4.35 (m,1H), 4.30-3.96 (m, 4H), 2.85-2.58 (m, 1H), 2.45 (s, 3H), 2.40-2.25 (m,1H), 1.58-1.42 (m, 5H), 1.40-1.30 (m, 5H), 1.07 (s, 9H), 1.00-0.80 (m,1H); LC-MS [M+23]⁺ 616.2

Step 4:8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propanoyl)piperidin-4-yl]ethyl}-9H-purin-6-amineand8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propanoyl)piperidin-4-yl]ethyl}-3H-purin-6-amine

The alkylation reaction was carried out according to the proceduredescribed for example 1 and 2 using8-(6-Bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine (0.172 g,0.47 mmol) and2-[1-((2R)-2-{[tert-butyl-(diphenyl)-silyl]-oxy}-propanoyl)-piperidin-4-yl]-ethyl4-methylbenzenesulfonate (0.280 g, 0.47 mmol) obtained from step 3 toafford 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-((2R)-2-{[tertbutyl(diphenyl)silyl]oxy}propanoyl)piperidin-4-yl]ethyl}-9H-purin-6-amine;LC-MS [M+1]⁺ 787.1 and8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propanoyl)piperidin-4-yl]ethyl}-3H-purin-6-amine;LC-MS [M+H]⁺ 787.1

Step 5:(2R)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-oland(2R)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol

To the mixture of8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propanoyl)piperidin-4-yl]ethyl}-9H-purin-6-amineand8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3-{2-[1-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propanoyl)piperidin-4-yl]ethyl}-3H-purin-6-amine.

(0.314 g, 0.398 mmol) in THF (5 mL), was added 1.0 M. THF solution oftetra-n-butylammonium fluoride (0.47 mL, 0.47 mmol) and stirred thereaction mixture at room temperature for over night. After completion ofreaction the reaction mixture was concentrated and purified bypreparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobilephase: solvent A: Water HPLC grade containing 0.01% TFA, and solvent B:acetonitrile containing 0.01% TFA, general eluting gradient—solvent B15% to 80 over 15 to 25 minutes run time]. After lyophilization of HPLCfractions N9 and N-3 isomers were isolated as trifluoroacetate salts.(2R)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol;LC-MS [M+H]⁺ 549.1 and(2R)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-oland LC-MS [M+H]⁺ 549.1.

Examples 768 and 769(2S)-1-(4-{2-[6-Amino-8-(2,3-dihydro-1-benzofuran-5-ylthio)-9H-purin-9-yl]ethyl}piperidin-1-yl)-1-oxopropan-2-oland(2S)-1-(4-{2-[6-amino-8-(2,3-dihydro-1-benzofuran-5-ylthio)-3H-purin-3-yl]ethyl}piperidin-1-yl)-1-oxopropan-2-ol

The title compounds were prepared by a procedure similar to examples 756and 757 using 8-(2,3-dihydro-benzofuran-5-ylsulfanyl)-9H-purin-6-ylamine(0.100 g, 0.350 mmol) and acetic acid(S)-1-methyl-2-oxo-2-{4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethylester (0.278 g, 0.700 mmol) to give the mixture of(1S)-2-(4-{2-[6-amino-8-(2,3-dihydro-1-benzofuran-5-ylthio)-9H-purin-9-yl]ethyl}piperidin-1-yl)-1-methyl-2-oxoethylacetate, LC-MS [M+H]⁺ 511.2 and(1S)-2-(4-{2-[6-amino-8-(2,3-dihydro-1-benzofuran-5-ylthio)-3H-purin-3-yl]ethyl}piperidin-1-yl)-1-methyl-2-oxoethylacetate, LC-MS [M+H]⁺ 511.2.

The above mixture was treated with LiOH.H₂O as described in example 62and 63, the isomers were separated by preparative HPLC.(2S)-1-(4-{2-[6-amino-8-(2,3-dihydro-1-benzofuran-5-ylthio)-9H-purin-9-yl]ethyl}piperidin-1-yl)-1-oxopropan-2-ol.¹H NMR (CD₃OD) δ 8.28 (s, 1H), 7.49 (s, 1H), 7.40 (dd, J=1.9, 8.2 Hz,1H), 6.84 (d, J=8.2 Hz, 1H), 4.62 (t, J=8.5 Hz, 2H), 4.59-4.42 (m, 2H),4.34 (t, J=7.4 Hz, 2H), 4.06-3.97 (m, 1H), 3.25 (t, J=8.5 Hz, 2H),3.10-2.98 (m, 1H), 2.70-2.39 (m, 1H), 1.96-1.74 (m, 4H), 1.70-1.55 (m,1H), 1.35-1.10 (m, 5H); TOF-MS [M+H]⁺ 469.2.(2S)-1-(4-{2-[6-amino-8-(2,3-dihydro-1-benzofuran-5-ylthio)-3H-purin-3-yl]ethyl}piperidin-1-yl)-1-oxopropan-2-ol.TOF-MS [M+H]⁺ 469.2

Examples 770 and 771(2S)-3-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-3-oxopropane-1,2-dioland(2S)-3-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-3-oxopropane-1,2-diol

Reagents: Barton's base, DMF, 90-100° C., 16 h; b) aq AcOH, rt, 12 h

Step 1: The alkylation reaction was carried out according to theprocedure described for example 1 and 2 using8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine (0.100 g,0.27 mmol) and toluene-4-sulfonic acid2-[1-((S)-2,2-dimethyl-[1,3]dioxolone-4-carbonyl)-piperidin-4-yl]-ethylester (0.224 g, 0.54 mmol) to give the mixture of8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl}piperidin-4-yl)ethyl]-3H-purin-6-amine,LC-MS [M+H]⁺ 605.2 and8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl}piperidin-4-yl)ethyl]-9H-purin-6-amine,LC-MS [M+H]⁺ 605.2. The crude mixture used in the next reaction withoutfurther purification.

Step 2: The crude mixture of8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3-[2-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl}piperidin-4-yl)ethyl]-3H-purin-6-amineand8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-[2-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl}piperidin-4-yl)ethyl]-9H-purin-6-aminefrom step 1 (0.31 g, 0.51 mmol) was dissolved in 60% aq. AcOH solution(5 mL) and the reaction mixture was allowed to stir for 12 hr. Thereaction mixture was neutralized using K₂CO₃ and evaporated thecontents. The residue was diluted with MeOH-DCM (1:2) (10 mL) andfiltered. The filtrate was evaporated under reduced pressure. Themixture was purified by preparative HPLC [X-Terra prep-RP18 10 um,19×250 mm (waters), Mobile phase: solvent A: Water HPLC grade containing0.01% TFA, and solvent B: acetonitrile containing 0.01% TFA, generaleluting gradient—solvent B 15% to 80 over 15 to 25 minutes run time].After lyophilization of HPLC fractions N-9 and N-3 isomers were isolatedas trifluoroacetate salts.(2S)-3-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-3-oxopropane-1,2-diol.TOF-MS [M+H]⁺ 565.09 and(2S)-3-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-3-oxopropane-1,2-diol.¹H NMR (CD₃OD) δ 8.34 (s, 1H), 7.28 (s, 1H), 7.22 (s, 1H), 6.09 (s, 2H),4.55-4.45 (m, 2H), 4.38 (t, J=7.0 Hz, 2H), 4.12-4.02 (m, 1H), 3.73-3.58(m, 2H), 3.12-3.00 (m, 1H), 2.70-2.60 (m, 1H), 1.95-1.55 (m, 5H),1.30-1.10 (m, 2H); TOF-MS [M+H]⁺ 565.09.

Example 772 tert-Butyl((1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethyl)carbamate

Reagents: a) Barton's base, THF, 100° C., MW, 15 min;

To a suspension of 8-bromoadenine (0.08 g, 0.367 mmol) andtoluene-4-sulfonic acid2-[1-((S)-2-tert-butoxycarbonylamino-propionyl)-piperidin-4-yl]-ethylester (0.200 g, 0.440 mmol) in THF was added Barton's base (91 μl, 0.40mmol) at room temperature. The reaction mixture was heated at 100° C.for 15 min in microwave reactor, at the end of this period reaction wascooled to room temperature and the crude was purified by Isco silica gelflash column using 0-30% gradient of EtOAc-Hexane to give tert-butyl{(1S)-2-[4-(2-{6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-3H-purin-3-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamateand tert-butyl{(1S)-2-[4-(2-{6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate(0.090 g, 49%)

Example 773 tert-Butyl{(1S)-2-[4-(2-{6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate

Reagents: a) 7-Chloro-2-mercaptobenzothiazole, (CH₃)₃COK, DMF, 130° C.,6 h;

To a suspension of 7-Chloro-2-mercaptobenzothiazole (0.020 g, 0.097mmol) in DMF (2.0 mL) was added (CH₃)₃COK (0.011 g, 0.97 mmol) at roomtemperature and stirring continued for 30 min. To the above reactionmixture tert-butyl((1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethyl)carbamate(0.040 g, 0.081 mmol) in (1 mL) of DMF was added at room temperature.The reaction mixture was heated to 130° C. for 6 h, at the end of thisperiod solvent was evaporated and crude was purified by preparative HPLC[X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobile phase: solvent A:Water HPLC grade containing 0.01% TFA, and solvent B: acetonitrilecontaining 0.01% TFA, general eluting gradient—solvent B 15% to 80 over15 to 25 minutes run time]. After lyophilization of HPLC fractions toafford title product. ¹H NMR δ (CD₃OD), 8.35 (s, 1H), 7.85-7.82 (m, 1H),7.50-7.40 (m, 2H), 4.40 (t, J=7.2 Hz, 2H), 4.00-3.90 (m, 2H), 1.80-1.70(m, 4H), 1.21-1.15 (m, 6H), 1.15 (s, 9H), 1.10 (s, 3H); LC-MS [M+H]⁺617.1

Example 7749-(2-{1-[(2S)-2-Aminopropanoyl]piperidin-4-yl}ethyl)-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-6-amine

To a solution of Boc protected product from example 773 in DCM was addedTFA and stirred at room temperature for 3 h. The solvent and excess TFAwas evaporated under reduced pressure and the residual TFA was removedby co-evaporating with toluene to give title product as trifluoroacetatesalt. ¹H NMR δ (CD₃OD), 8.35 (s, 1H), 7.84-7.82 (m, 1H), 7.50-7.40 (m,2H), 4.40 (t, J=7.2 Hz, 2H), 4.00-3.90 (m, 1H), 1.80-1.70 (m, 4H),1.41-1.37 (m, 4H), 1.32-1.30 (m, 3H), 1.20 (s, 3H); LC-MS [M+H]⁺ 517.1

Example 775(2S)-1-[4-(2-{6-Amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol

Step 1:(1S)-2-{4-[2-(6-Amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethylacetate

The title compound was prepared according to the procedure described forexamples 756 and 757 (step 1) using acetic acid(S)-1-methyl-2-oxo-2-{4-[2-(toluene-4-sulfonyloxy)-ethyl]-piperidin-1-yl}-ethylester and 8-bromoadenine to give the mixture of(1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethylacetate and(1S)-2-{4-[2-(6-amino-8-bromo-3H-purin-3-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethylacetate. This mixture was purified by Isco silica gel flash column usingEtOAc to give(1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethyl acetate. LC-MS [M+H]⁺ 439.1

Step 2:(1S)-2-[4-(2-{6-Amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethylacetate

The title product was prepared according to the procedure described forexample 81 using(1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethylacetate and 7-chloro-2-mercaptobenzothiazole. LC-MS [M+H]⁺ 562.1, alongwith hydrolyzed product, the mixture was used for the next step withoutany further purification.

Step 3:(2S)-1-[4-(2-{6-Amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol

The crude product from Step 2 was suspended in methanol and K₂CO₃ wasadded and stirring continued for 2 h. The title product was isolatedafter preparative HPLC purification as a trifluoroacetate salt. LC-MS[M+H]⁺ 518.1

Examples 776 and 7779-{2-[1-(1-Acetyl-L-prolyl)piperidin-4-yl]ethyl}-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amineand3-{2-[1-(1-acetyl-L-prolyl)piperidin-4-yl]ethyl}-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine

The title compounds were prepared according to the procedure describedfor examples 1 and 2 using8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine andtoluene-4-sulfonic acid2-[1-[(S)-1-acetyl-pyrrolidine-2-carbonyl)-piperidin-4-yl]-ethyl ester.The products are isolated as trifluoroacetate salts after preparativeHPLC purification and lyophilization of HPLC fractions.9-{2-[1-(1-Acetyl-L-prolyl)piperidin-4-yl]ethyl}-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine¹H NMR (CD₃OD) δ 8.28 (s, 1H), 7.28 (s, 1H), 7.19 and 7.17 (s, 1H), 6.09(s, 2H), 4.47 (m, 1H), 4.37 (t, J=7.2 Hz, 2H), 4.04 (m 1H), 3.67-3.56(m, 2H), 3.15 (m, 1H), 2.64 (m, 1H), 2.23 (m, 1H), 2.08 and 2.076 (s,3H), 2.06-1.96 (m, 2H), 1.91-1.78 (m, 6H), 1.62 (m, 1H), 1.23 (m, 1H),1.11 (m, 1H); LC-MS [M+H]⁺ 616.1.3-{2-[1-(1-Acetyl-L-prolyl)piperidin-4-yl]ethyl}-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-6-amine.LC-MS [M+H]⁺ 616.1

Examples 778 and 779

tert-Butyl{(1S)-2-[3-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamateand tert-butyl{(1S)-2-[3-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate

The title compounds were prepared according to the procedure describedfor examples 1 and 2 using8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine andtoluene-4-sulfonic acid1-((S)-2-tert-butoxycarbonylamino-propionyl)-piperidin-3-ylmethyl ester.The products isolated as a trifluoroacetate salt. tert-Butyl{(1S)-2-[3-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}methyl)piperidin-1-yl]-[1-methyl-2-oxoethyl}carbamate.LC-MS [M+H]⁺ 634.5 and tert-butyl{(1S)-2-[3-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate.LC-MS [M+H]⁺ 634.5

Examples 780

9-({1-[(2S)-2-Aminopropanoyl]piperidin-3-yl}methyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine

The title compound was prepared according to the procedure described forexample 50 using tert-butyl{(1S)-2-[3-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamateand isolated as trifluoroacetate salt. LC-MS [M+H]⁺ 534.4

Examples 781 and 782

tert-Butyl{(1R)-2-[4-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamateand tert-butyl{(1R)-2-[4-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate

The title compounds were prepared according to the procedure describedfor examples 1 and 2 using8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine andToluene-4-sulfonic acid1-((R)-2-tert-butoxycarbonylamino-propionyl)-piperidin-4-ylmethyl ester.Title compounds were isolated as a trifluoroacetate salt afterpreparative HPLC purification. tert-Butyl{(1R)-2-[4-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate.LC-MS [M+H]⁺ 634.5 and tert-butyl{(1R)-2-[4-({6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-3H-purin-3-yl}methyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate.LC-MS [M+H]⁺ 634.5

Activity Examples

Binding Assay

Compound binding to purified Hsp90 was monitored using BODIPY-labeledgeldanamycin (BODIPY-GM) in a fluorescence polarization assay adaptedfrom Kim et al. (Journal of Biomolecular Screening 2004, 9(5):375-381).Compound dilutions (in 100% DMSO) were added to black-bottom 96-wellplates (Greiner; 2% DMSO final), and equal volumes of BODIPY-GM (10 nMfinal) and purified human Hsp90 (Stressgen, SPP-770; 30 nM final) inassay buffer (20 mM HEPES-KOH pH 7.3, 50 mM KCl, 5 mM MgCl₂, 20 mMNa₂MoO₄, 0.01% NP-40, 0.1 mg/mL bovine gamma globulin [Invitrogen,P2045], 2 mM DTT) were added sequentially to yield a final volume of 50microliters. Plates were incubated overnight at room temperature.Parallel and perpendicular fluorescence measurements were read (LJLBioSystems Analyst AD plate reader) with excitation/emission wavelengthsof 485/530 nm. Background fluorescence (buffer only) was subtracted, andfluorescence polarization (FP) values, expressed in mP units, werecalculated from parallel and perpendicular fluorescence readings asfollows:FP=(parallel−perpendicular)/(parallel+perpendicular)*1000

Percent inhibition was calculated by normalizing the FP values to thoseobtained in parallel reactions containing DMSO and subtracting thesenormalized values from 100%. Intrinsic compound fluorescence wasindependently monitored, and FP data points confounded by compoundfluorescence were excluded from the analysis.

Her2-Luciferase Assay

HCT116 cells stably transfected with a Her2 (kinase domain)-Luciferasefusion were seeded into black 96-well plates at 10,000 cells per well in100 microliters (DMEM supplemented with 10% serum) and incubatedovernight. Compound dilutions (in 100% DMSO) were added to individualwells (0.4% DMSO final), and plates were incubated for four hours.Plates were equilibrated to room temperature (5 min), 100 microlitersSteady-Glo reagent (Promega #E2520) was added per well, and plates wereincubated at room temperature for 5 minutes. Luminescence was thenmeasured (TopCount, Perkin-Elmer).

Cytotoxicity Assay

HCT116 cells were seeded into black 96-well plates at 5,000 cells perwell in 100 microliters (DMEM supplemented with 10% serum) and incubatedovernight. Compound dilutions (in 100% DMSO) were added to individualwells (0.4% DMSO final), and plates were incubated for 72 hours. Plateswere equilibrated to room temperature (5 min). Fifty microliters lysisbuffer followed by 50 microliters substrate

solution (ATPLite [2 step], Perkin-Elmer, #601941) were added to eachwell, and plates were incubated at room temperature 5 minutes.Luminescence was then measured (TopCount, Perkin-Elmer). TABLE 18 %Inhibition at 5 μM Compound Example Concentration IC50 (μM) 1 0.34 23.47 3 36 4 75 0.65 5 8 6 66 1.06 7 22 8 18.0 9 1.0 10 >50 11 0.6 12 >1013 0.045 14 5.0 15 6.5 16 6 17 >10 18 0 19 >10 20 0 >10 21 >10 22 >1023 >10 24 >10 25 0.041 26 >10 27 >10 28 0 29 0.15 30 16 >10 31 >1032 >10 33 0.017 34 >10 35 0.80 36 >5 37 0.8 38 >10 39 0.23 40 >10 410.50 42 >5 43 0.70 44 27 45 8.1 46 >10 47 >10 48 >10 49 55 1.2 50 3 5152 1.5 52 0 53 0.045 46 >10 47 >10 48 >10 49 55 1.2 50 3 51 52 1.5 52 053 0.045 46 >10 47 >10 48 >10 49 55 1.2 50 3 51 52 1.5 52 0 53 0.04546 >10 47 >10 48 >10 49 55 1.2 50 3 51 52 1.5 52 0 53 0.045 54 13 55 1.756 3 57 0.4 58 8 59 >25 60 30 61 >10 62 >10 63 >5 64 >5 65 61 0.50 66 567 56 1.5 68 0 69 69 0.25 70 7 71 41 >25 72 0 73 2 >3 74 0 75 2.9 76 677 1.9 78 17 79 0.30 80 10 81 23 82 5 83 0 84 0 >5 85 0.36 86 >5 87 1288 1.3 89 >10 90 6 91 0.2 92 0 93 0.19 94 0 95 >3 96 2 97 0.45 98 0 990.3 100 39 101 >3 102 39 103 >1 104 38 105 >1 106 41 107 0 108 30 1090.3 110 16 111 10.00 112 0 113 0.55 114 14 115 0.110 116 0 117 54 0.30118 0 119 15 120 0 121 54 0.52 122 0.085 123 0 124 0.22 125 12 126 0.30127 51 128 0.066 129 54 130 0.04 131 18 132 54 0.50 133 0 134 >3 135 1.3136 16 137 0.210 138 0 139 0.09 140 0 141 0.04 142 0 143 >3 144 0 145 >3146 0 147 0.044 148 35 149 0.07 150 0 151 0.05 152 20 153 0.60 154 >10155 0.095 156 16 157 58 0.50 158 0 159 63 0.80 160 0 161 17 0.32 162 0163 >10 164 0 165 60 0.30 166 0 167 44 >25 168 0 169 37 0.470 170 3171 >25 172 >10 173 44 >25 174 37 >25 175 46 14.00 135 1.3 136 16 1370.210 138 0 139 0.09 140 0 141 0.04 142 0 143 >3 144 0 145 >3 146 0 1470.044 148 35 149 0.07 150 0 151 0.05 152 20 153 0.60 154 >10 155 0.095156 16 157 58 0.50 158 0 159 63 0.80 160 0 161 17 0.32 162 0 163 >10 1640 165 60 0.30 166 0 167 44 >25 168 0 169 37 0.470 170 3 171 >25 172 >10173 44 >25 174 37 >25 175 46 14.00 176 6 177 0 178 9 179 8 180 >10181 >25 182 >10 183 100 1.100 184 0 185 >2.5 186 0 187 >2.5 188 21189 >8 190 8 191 >8 192 0 193 39 0.31 194 0 195 80 0.079 196 10 1970.170 198 18 199 0.110 200 18 201 0.072 202 9 203 0.09 204 11 205 800.240 206 0 207 0.038 208 46 >25 209 0.45 210 8 211 >25 212 4 213 520.310 214 0.950 215 0 216 78 >8 217 >10 218 >3 219 >8 220 2 221 >9 22271 0.062 223 0.50 224 >5 225 >25 226 >25 227 0 228 >8 229 24 230 0.210231 >25 232 >25 233 0.500 234 0 235 >8 236 0 237 >25 238 >25 239 >25240 >8 241 0 242 ND 243 >1 244 ND 245 1 246 ND 247 3.0 248 >5 249 0.100250 0.900 251 0.075 252 >25 253 >8 254 >8 255 0.250 256 0.470 257 >25258 >25 259 12.0 260 1.50 261 >25 262 >25 263 >25 264 ND 265 20 266 12.0267 >25 268 7.0 269 5.50 270 7.0 271 >25 272 16 273 1.30 274 0.0275 >3.0 276 0.0 277 >8.0 278 1.0 279 >25.0 280 0.0 281 0.120 282 0.055283 12.0 284 3.0 285 1.30 286 3.0 287 0.06 288 4.00 289 1.60 290 0.07291 0.0 292 >25.0 293 0.0 294 >25.0 295 0.0 296 0.350 297 8.0 298 >25.0299 0.0 300 0.400 301 5.0 302 >25.0 303 21.0 304 >25.0 305 29.0306 >25.0 307 40.0 308 0.180 309 25.0 310 >25.0 311 0.0 312 >25 313 3.0314 6.80 315 21.0 316 18.0 317 0.0 318 7.0 319 27.0 320 0.240 321 49.0322 0.100 323 0.0 324 2.80 325 0.0 326 0.035 327 33.0 328 >8.0 329 25.0330 0.070 331 25.0 332 1.00 333 43.0 334 2.30 335 3.00 336 13.0 337 >8338 0 339 0.115 340 23 341 0.200 342 19 343 0 344 22 345 3 346 0.325 3472.5 348 0.800 349 12 350 25 351 8 352 35 353 0.057 354 0.250 355 >25356 >25 357 0 358 0.450 359 3 360 5 361 2.90 362 >25 363 0.300 364 0.102365 31 366 20 367 >25 368 *Fluorescent 369 0.035 370 0.600 371 0.700 3720.100 373 15 374 >25 375 >1 376 0 377 *Fluorescent 378 0.240 379 9.80380 4 381 0.390 382 0.140 383 21 384 >1 385 ND ND 386 0.110 387 >8 38813 389 38 390 0.310 391 1.2 392 2.9 393 0 394 0.700 395 0 396 0.810 3971 398 0.140 399 0.950 400 6.0 401 2 402 0.590 403 14 404 ND ND 405 >8406 >25 407 >25 408 ND ND 409 0.130 410 11 411 0.200 412 0 413 28 4140.54 415 0.46 416 0.200 417 0 418 0.300 419 2.90 420 7 421 28 422 >3 4230 424 0.152 425 6 426 0.150 427 32 428 >8 429 3.8 430 15 431 0.130 4320.065 433 0.125 434 0.037 435 0.195 436 0.390 437 0.390 438 ND ND 439 24440 60 441 45 442 4 443 36 444 1.10 445 0.305 446 4 447 0.210 448 45 4490.200 450 57 451 0.195 452 21 453 0.700 454 0.305 455 0.060 456 ND457 >2.00 458 0.380 459 18 460 2.80 461 15 462 7.90 463 14% 464 0.40 4650.470 466 0.060 467 0 468 9 469 8.8 470 0.280 471 0.600 472 0.070 4730.035 474 0.140 475 0.172 476 0.090 477 0.467 478 0.140 479 0.199 4800.160 481 0.050 482 0.0 483 0.184 484 0.600 485 1 486 7 487 0.900 488 29489 1.40 490 25 491 0.039 492 0.900 493 8.9 494 5.5 495 6 496 0.081 49725 498 0.525 499 21 500 0.060 501 ND 502 0.140 503 0.190 504 ND 5050.085 506 ND 507 0.405 508 ND 509 ND 510 0.250 511 ND 512 0.110 513 ND514 0.110 515 ND 516 0.600 517 ND 518 0.140 519 ND 520 >2.00 521 ND 5220.053 523 ND 524 0.100 525 13.00 526 0.300 527 19.00 528 >5.00 529 ND530 2.50 531 ND 532 5.00 533 0.00 534 5.00 535 1.00 536 >5.00 537 >5.00538 1.60 539 >5.00 540 >5.00 541 4.00 542 >5.00 543 0.00 544 1.40 5450.050 546 >5.00 547 12.00 548 >5.00 549 11.00 550 >5.00 551 0.00 552 ND553 >5.00 554 0.00 555 0.700 556 2.00 557 1.50 558 >5.00 559 >5.00560 >5.00 561 >5.00 562 ND 563 >5.00 564 >2.00 565 >5.00 566 1.00567 >5.00 568 0.00 569 >5.00 570 0.00 571 >5.00 572 0.00 573 1.40 5741.80 575 0.80 576 31 577 0.140 578 0.550 579 0.310 580 0.400 581 0.240582 0.900 583 55.00 584 1.40 585 0.600 586 0.450 587 ND 588 >2.00 589 ND590 0.500 591 ND 592 >5.00 593 ND 594 0.270 595 43.00 596 ND 597 0.310598 ND 599 0.260 600 ND 601 >8.00 602 31.00 603 4.00 604 0.190 605 0.056606 49.00 607 0.062 608 5.00 609 0.045 610 0.088 611 22.00 612 0.230 61315.00 614 1.80 615 13.00 616 0.090 617 83.00 618 0.041 619 76.00 6200.170 621 >5.00 622 >5.00 623 >4.00 624 0.580 625 0.110 626 ND 627 >8.00628 23.00 629 >25.00 630 9.00 631 2.00 632 >3.00 633 1.50 634 8.10 6352.10 636 25.00 637 >25.00 638 >25.00 639 0.900 640 19.00 641 1.10 64215.00 643 5.00 644 0.200 645 0.450 646 0.060 647 ND 648 0.684 649 ND650 >2.00 651 >5.00 652 0.00 653 >2.00 654 2.00 655 >5.00 656 >5.00 6570.190 658 >5.00 659 4.00 660 >5.00 661 0.060 649 ND 650 >2.00 651 >5.00652 0.00 653 >2.00 654 2.00 655 >5.00 656 >5.00 657 0.190 658 >5.00 6594.00 660 >5.00 661 0.060 662 0.300 663 15 664 *Fluorescent 665 0 6660.800 667 0 668 4.8 669 10 670 1.6 671 1.0 672 0.9 673 0 674 0.08 675 49676 0.95 677 ND 678 *Fluorescent 679 ND 680 14 681 1.0 682 0.19 683 5684 685 686 ND 687 0.080 688 30 689 0.120 690 0.29 691 0.125 692 2.00693 0.059 695 0.410 697 0.600 698 55 699 0.600 701 0.200 703 0.190 7050.080 707 0.070 709 0.230 711 0.600 713 0.495 715 >2 717 0.200 719 0.800720 ND 722 0.130 723 ND 724 0.105 725 0.100 726 26 727 32 728 0.200730 >5 731 1.0 732 >5 734 >2 736 ND 738 ND 740 >5 741 ND ND 742 0.140743 0.040 744 0.068 745 0.123 746 0.240 747 0.110 748 0.210 749 0.330750 0.180 751 0.195 752 0.130 753 0.059 754 0.050 755 0.140 756 ND 7570.205 760 0.325 761 ND ND 764 ND 765 ND 766 ND 767 ND 768 >5 769 ND 7710.120 772 >5 773 0.390 774 0.200 775 1.80 776 0.310 778 2.00 779 43.00780 ND 781 ND 782 ND*Compound is active in Luciferase refolding assayND—not determined

1. A compound of Formula I below or a pharmaceutically acceptable saltthereof

wherein: A is chosen from a substituted or unsubstituted aryl,heteroaryl, heterocyclic, or carbocyclic group; B is chosen from asubstituted or unsubstituted aryl, heteroaryl, heterocyclic, orcarbocyclic group; R1 is chosen from hydro, alkyl, aryl, heteroaryl,amino, halo, sulfur, and thioalkyl. L₁ can be saturated, partiallysaturated, or unsaturated, and is chosen from —(CH₂)_(n)—(CH₂)_(n)—,—(CH₂)_(n)C(═O)(CH₂)_(n)—, —(CH₂)_(n)C(═O)N(CH₂)_(n)—,—(CH₂)_(n)NC(═O)O(CH₂)_(n)—, —(CH₂)_(n)NC(═O)N(CH₂)_(n)—,—(CH₂)_(n)NC(═S)S(CH₂)_(n)—, —(CH₂)_(n)OC(═O)S(CH₂)—,—(CH₂)_(n)NH(CH₂)_(n)—, —(CH₂)_(n)O(CH₂)_(n)—, —(CH₂)_(n)S(CH₂)_(n)—,and —(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n is independently chosenfrom 0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon and/ornitrogen can be optionally substituted with one or more substituentsindependently chosen from hydroxyl, halo, alkoxy, alkyl, amino,cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl, aryl, cycloalkyl,and heterocyclic; wherein —R₂ and —R₃ are independently chosen from —H,alkyl, and —C(═O)OR₄; and wherein R₄ is an alkyl group (e.g., methyl,ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl); L₂ can besaturated, partially saturated, or unsaturated, and is chosen from—(CH₂)_(n)—(CH₂)_(n)—, —(CH₂)_(n)C(═O)(CH₂)_(n)—,—(CH₂)_(n)C(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═O)O(CH₂)_(n)—,—(CH₂)_(n)NC(═O)N(CH₂)_(n)—, —(CH₂)_(n)NC(═S)S(CH₂)_(n)—,—(CH₂)_(n)OC(═O)S(CH₂)_(n)—, —(CH₂)_(n)NH(CH₂)_(n)—,—(CH₂)_(n)O(CH₂)_(n)—, —(CH₂)_(n)S(CH₂)_(n)—, and—(CH₂)_(n)NC(═S)N(CH₂)_(n)—, where each n is independently chosen from0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon and/or nitrogencan be optionally substituted with one or more substituentsindependently chosen from hydroxyl, halo, alkoxy, alkyl, amino,cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl, aryl, cycloalkyl,and heterocyclic; wherein —R₂ and —R₃ are independently chosen from —H,alkyl, and —C(═O)OR₄; and wherein R₄ is an alkyl group (e.g., methyl,ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl); andpharmaceutically acceptable salts thereof.
 2. The compound of claim 1wherein A is an aryl group having one or more substituents chosen fromhalo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl,hydroxyl, —C≡N, —SO₃, and —COOH.
 3. The compound of claim 1, wherein Ais a phenyl group having one or more substituents chosen from halo,alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —C(═O)alkyl, hydroxyl, and—COOH.
 4. The compound of claim 1, wherein A is an aryl group with oneor more substituents chosen from hydroxyl, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂, —NH(C₁₋₃ alkyl), —C(═O)NH₂,—C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂, —S(═O)₂(C₁₋₃alkyl),—S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃ alkyl), —CHF₂, —OCF₃,—OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, and —NO₂.
 5. The compound of claim 1,wherein A is a phenyl group having from 1-5 substituents independentlychosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio,alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy,aryloxy, arylthio, carbocycle, cyano, cyanato, halo, haloalkyl,halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido. 6.The compound of claim 1 wherein B is an aryl group having one or moresubstituents chosen from halo, alkyl, alkoxy, haloalkyl, haloalkoxy,nitro, —C(═O)alkyl, hydroxyl, —SO₃, and —COOH.
 7. The compound of claim1 wherein B is an aryl group with one or more substituents chosen fromhydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C₁₋₃ alkyl)₂,—NH(C₁₋₃ alkyl), —C(═O)NH₂, —C(═O)NH(C₁₋₃ alkyl), —C(═O)N(C₁₋₃ alkyl)₂,—S(═O)₂(C₁₋₃alkyl), —S(═O)₂NH₂, —S(═O)₂N(C₁₋₃ alkyl)₂, —S(═O)₂NH(C₁₋₃alkyl), —CHF₂, —OCF₃, —OCHF₂, —SCF₃, —CF₃, —CN, —NH₂, —SO₃, and —NO₂. 8.The compound of claim 1 wherein B is a phenyl group having from 1-5substituents independently chosen from acylamino, acyloxy, alkenyl,alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl,arylalkynyl, arylalkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato,halo, haloalkyl, halophenyl, hydroxyl, heteroaryl, heteroaryloxy,heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro,sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato,trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, and C-amido.
 9. The compound of claim 1 wherein A is asubstituted or unsubstituted indanone group.
 10. The compound of claim 9wherein A has from 1-5 substituents independently chosen from acylamino,acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl,arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio,carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxyl,heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy, isocyanato,isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl,thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl,O-thiocarbamyl, N-thiocarbamyl, and C-amido.
 11. The compound of claim1, wherein A is a substituted or unsubstituted indane group.
 12. Thecompound of claim 11, wherein A has from 1-5 substituents independentlychosen from acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio,alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy,aryloxy, arylthio, carbocycle, cyano, cyanato, halo, haloalkyl,halophenyl, hydroxyl, heteroaryl, heteroaryloxy, heterocycle,heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl,sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido. 13.The compound of claim 1 wherein B is a homopiperidine group.
 14. Thecompound of claim 1 wherein B is a homopiperidine group substituted withone or more substituents chosen from hydro, halo, alkyl, alkoxy,haloalkyl, haloalkoxy, nitro, —CH₂-aryl, —C(═O)alkyl, —C(═O)cycloalkyl,—C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃, —COOH (and esters thereof),amino acid (chosen from natural and non-natural amino acids), peptidehaving 1-5 amino acid residues (chosen from natural and non-naturalamino acids), —C(═O)alkyl where the alkyl is substituted with one ormore substituents (chosen from alkyl, amino, alkoxy, haloalkyl,haloalkoxy, nitro, cyano, hydroxyl, —COOH (and esters thereof),sulfonyl, sulfonamide) and sulfonyl.
 15. The compound of claim 1,wherein B is a homopiperidine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃,—COOH (and esters thereof), and sulfonyl.
 16. The compound of claim 1,wherein B is a homopiperidine group having one or more substituentschosen from —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.
 17. The compound of claim 1 wherein Bis a piperidine group.
 18. The compound of claim 1 wherein B is apiperidine group substituted with one or more substituents chosen fromhydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl,—SO₃, —COOH (and esters thereof), amino acid (chosen from natural andnon-natural amino acids), peptide having 1-5 amino acid residues (chosenfrom natural and non-natural amino acids), —C(═O)alkyl where the alkylis substituted with one or more substituents (chosen from alkyl, amino,alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxyl, —COOH (and estersthereof), sulfonyl, sulfonamide) and sulfonyl.
 19. The compound of claim1, wherein B is a piperidine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃,—COOH (and esters thereof), and sulfonyl.
 20. The compound of claim 1,wherein B is a piperidine group having one or more substituents chosenfrom —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.
 21. The compound of claim 1 wherein Bis a piperazine group.
 22. The compound of claim 1 wherein B is apiperazine group substituted with one or more substituents chosen fromhydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl,—SO₃, —COOH (and esters thereof), amino acid (chosen from natural andnon-natural amino acids), peptide having 1-5 amino acid residues (chosenfrom natural and non-natural amino acids), —C(═O)alkyl where the alkylis substituted with one or more substituents (chosen from alkyl, amino,alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxyl, —COOH (and estersthereof), sulfonyl, sulfonamide) and sulfonyl.
 23. The compound of claim1, wherein B is a piperazine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃,—COOH (and esters thereof), and sulfonyl.
 24. The compound of claim 1,wherein B is a piperazine group having one or more substituents chosenfrom —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.
 25. The compound of claim 1 wherein Bis a pyrrolidine group.
 26. The compound of claim 1 wherein B is apyrrolidine group substituted with one or more substituents chosen fromhydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl,—SO₃, —COOH (and esters thereof), amino acid (chosen from natural andnon-natural amino acids), peptide having 1-5 amino acid residues (chosenfrom natural and non-natural amino acids), —C(═O)alkyl where the alkylis substituted with one or more substituents (chosen from alkyl, amino,alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxyl, —COOH (and estersthereof), sulfonyl, sulfonamide) and sulfonyl.
 27. The compound of claim1, wherein B is a pyrrolidine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃,—COOH (and esters thereof), and sulfonyl.
 28. The compound of claim 1,wherein B is a pyrrolidine group having one or more substituents chosenfrom —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.
 29. The compound of claim 1, whereinB is an azetidine group.
 30. The compound of claim 1, wherein B is anazetidine group substituted with one or more substituents chosen fromhydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —CH₂-aryl,—C(═O)alkyl, —C(═O)cycloalkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl,—SO₃, —COOH (and esters thereof), amino acid (chosen from natural andnon-natural amino acids), peptide having 1-5 amino acid residues (chosenfrom natural and non-natural amino acids), —C(═O)alkyl where the alkylis substituted with one or more substituents (chosen from alkyl, amino,alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxyl, —COOH (and estersthereof), sulfonyl, sulfonamide) and sulfonyl.
 31. The compound of claim1, wherein B is an azetidine group having one or more substituentschosen from hydro, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro,—CH₂-aryl, —C(═O)alkyl, —C(═O)—NH-Alkyl, cycloalkyl, hydroxyl, —SO₃,—COOH (and esters thereof), and sulfonyl.
 32. The compound of claim 1,wherein B is an azetidine group having one or more substituents chosenfrom —C(═O), —C(═O)CH₃, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —C(═O)OCH₂CH₃,—S(═O)₂CH₃, —S(═O)₂CF₃, —C(═O)OC(CH₃)₃, —C(═O)OCH₂-phenyl, —CH₂-phenyl,—CH(CH₃)₂, —C(═O)NHCH₂CH₃, —C(═O)NHCH(CH₃)₂, —C(═O)NHC(CH₃)₃,—C(═O)NHCH₂C(═O)OCH₂CH₃, —C(═O)C(CH₃)₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂,—C(═O)CH₂C(CH₃)₃, and cyclopentyl.
 33. The compound of claim 1, whereinL₁ is —S—.
 34. The compound of claim 1, wherein L₂ is—(CH₂)_(n)—(CH₂)_(n)—, and each n is independently chosen from 0, 1, 2,and 3 and wherein each carbon can be optionally substituted with one ormore substituents independently chosen from hydroxyl, halo, alkoxy,alkyl, amino, cycloalkyl, —NR₂R₃, —NSO₂R₄, —NC(═O)NR₂R₃, heteroaryl,aryl, cycloalkyl, and heterocyclic; wherein —R₂ and —R₃ areindependently chosen from —H, alkyl, and —C(═O)OR₄; and wherein R₄ is analkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ortert-butyl).
 35. The compound of claim 1, wherein R1 is hydro.
 36. Acompound chosen from9-[2-(1-Acetylpiperidin-4-yl)ethyl]-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine,4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde,4-(2-{6-Amino-8-[(7-bromo-2,3-dihydro-1,4-benzodioxin-6-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde,9-(3-Amino-3-cyclopropylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine,9-(3-Amino-3-cyclohexylpropyl)-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-6-amine,(2S)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-ol,4-(2-{6-Amino-8-[(1-oxo-2,3-dihydro-1H-inden-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde,2-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-oxoethanol,and6-({9-[2-(1-Acetylpiperidin-4-yl)ethyl]-6-amino-9H-purin-8-yl}thio)-1,3-benzodioxole-5-carbonitrile.37. A compound chosen from8-(2,5-dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(2,4-dimethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,4-dimethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(4-chloro-phenylsulfonyl)-9-phenethyl-9H-purin-6-ylamine,8-(4-chloro-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,4-(6-amino-9-phenethyl-9H-purin-8-ylsulfanyl)-benzonitrile,4-(6-amino-3-phenethyl-3H-purin-8-ylsulfanyl)-benzonitrile,9-[2-(3,4-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(3,4-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine,9-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2,4-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2,4-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenyl-sulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,9-[2-(4-chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(4-chloro-phenyl)-ethyl]-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(-6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-chloro-2-fluorophenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pentafluorophenyl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-phenyl-propyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-phenyl-propyl)-3H-purin-6-ylamine,9-phenethyl-8-(3,4,5-trimethoxy-phensulfanyl)-9H-purin-6-ylamine,3-phenethyl-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(3-phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-9H-purin-6-ylamine.3-(3-phenyl-propyl)-8-(3,4,5-trimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-pyrrol-1-yl-propyl)-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-pyrrol-1-yl-propyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-chloro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-chloro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-phenyl-butyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-methoxy-phenyl)-cyclopropylmethyl]-3H-purin-6-ylamine,9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone,1-(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyrrol-1-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-pyrrol-1-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine,9-[2-(4-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(4-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2,3-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2,3-dichloro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,4-{2-[6-Amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenol,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzoicacid,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzoicacid,8-(2,5-dimethoxy-phenylsulfanyl)-3-(4-fluoro-benzyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(4-nitro-benzyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-phenyl)-butyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,4,6-trimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,4,6-trimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclobutylmethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[1-(4-chloro-phenyl)-cyclobutylmethyl]-3H-purin-6-ylamine,9-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(4-chloro-2-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-cyclopentyl-2-phenyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-cyclopentyl-2-phenyl-ethyl)-3H-purin-6-ylamine,9-(2-cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-cyclopentyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-pentyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-pentyl)-3H-purin-6-ylamine,2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)ethanol,2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)ethanol,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-Dimethoxy-phenylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3H-purin-6-ylamine,9-[2-(4-Chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,3-[2-(4-chloro-phenyl)-3-methyl-butyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine,9-[2-(2,4-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,9-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purine-6-ylamine,3-[2-(2-chloro-6-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purine-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,5-dimethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,5-dimethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-methyl-2-phenyl-butyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(3-methyl-2-phenyl-butyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3,5-dimethyl-phenyl)-ethyl]-9H-purine-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3,5-dimethyl-phenyl)-ethyl]-3H-purine-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyridin-4-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pyridin-2-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-Dimethoxy-phenylsulfanyl)-3-(2-pyridin-2-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine,9-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-chloro-4-fluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-bromo-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(3,5-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2,3-difluoro-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(6-Bromo-1,3-benzodioxol-5-ylsulfanyl)-9-[2-(2-fluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-fluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2-bromo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2-bromo-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-pyridin-3-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-pyridin-3-yl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-iodo-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-iodo-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-o-tolyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-o-tolyl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-naphthalen-1-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-naphthalen-1-yl-ethyl)-3H-purin-6-ylamine,1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-ethanone,1-(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-ethanone,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(2,3-difluoro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-1,3-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(2,3-difluoro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-p-tolyl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-p-tolyl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine,9-(2-benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-benzo[1,3]dioxol-5-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxyphenyl-sulfanyl)-9H-purin-6-ylamine,3-(2-cyclohexyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,3-(2-biphenyl-4-yl-ethyl)-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3H-purin-6-ylamine,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-benzenesulfonicacid,4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-benzenesulfonicacid,2-[6-Amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-1-(2,4-dichloro-phenyl)-ethanol,2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-1-(2,4-dichloro-phenyl)-ethanol,9-(2-Cyclohexyl-2-phenyl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-cyclohexyl-2-phenyl-ethyl)-8-(25-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-(2-biphenyl-4-yl-ethyl)-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-trifluoromethyl-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-trifluoromethyl-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(4-dimethylamino-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(4-dimethylamino-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-diethoxy-phenylsulfanyl)-9-phenethyl-9H-purin-6-ylamine,8-(2,5-diethoxy-phenylsulfanyl)-3-phenethyl-3H-purin-6-ylamine,9-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(2-chloro-phenyl)-ethyl]-8-(2,5-diethoxy-phenylsulfanyl)-3H-purin-6-ylamine,9-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,3-[2-(3,5-dimethoxy-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[2-(3,5-dimethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3,5-dimethoxy-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-3-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-3-yl-ethyl)-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(2-thiophen-2-yl-ethyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-(2-thiophen-2-yl-ethyl)-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(2-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-3-[2-(2-nitro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylmethyl)-9-phenethyl-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylmethyl)-3-phenethyl-3H-purin-6-ylamine,(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester,(4-{2-[6-amino-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-3-yl]-ethyl}-phenyl)carbamicacid tert-butyl ester,9-[2-(4-amino-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-9-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester,(4-{2-[6-amino-8-(2,5-dimethoxy-phenylsulfanyl)-purin-3-yl]-ethyl}-phenyl)-carbamicacid tert-butyl ester,9-[2-(4-amino-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-trifluoromethoxy-phenyl)-ethyl]-9H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-(2-pentafluorophenyl-ethyl)-9H-purin-6-ylamine,9-[2-(3,5-bistrifluoromethyl-phenyl)-ethyl]-8-(2,5-dimethoxy-phenylsulfanyl)-9H-purin-6-ylamine,9-[2-(3,5-Bistrifluoromethyl-phenyl)-ethyl]-8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-[1-(4-chloro-phenyl)-cyclopropylmethyl]-9H-purin-6-ylamine,8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-3-[2-(3-nitro-phenyl)-ethyl]-3H-purin-6-ylamine,8-(2,5-dimethoxy-phenylsulfanyl)-9-[2-(3-nitro-phenyl)-ethyl]-9H-purin-6-ylamine,8-(benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one,and8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-phenethyl-1,9-dihydro-purin-6-one.